Leptin promotes proliferation and invasion of osteosarcoma cells by upregulating the expression of SIRT1

Osteosarcoma (OS) is a primary high-grade malignant bone neoplasm, and the prognosis of OS remains poor due to early metastasis. Leptin plays an essential role in tumorigenesis, but the role of leptin in the development of OS is still not fully understood. In this study, we used a human osteosarcoma MG-63 cell line as an experimental model. MG-63 cells were treated with leptin, and cell proliferation, apoptosis, adhesion, invasion, and gene expression, were evaluated. The results showed that leptin promoted proliferation, decreased adhesion, suppressed apoptosis, and promoted invasion, of MG-63 cells. Moreover, the expression of SIRT1 was upregulated in MG-63 cells exposed to leptin. Furthermore, MMP-2, 8, and 9 were significantly upregulated by SIRT1, while SIRT1 knockdown inhibited the proliferation and invasion of MG-63 cells. In conclusion, our results suggest that leptin promotes OS cell proliferation and invasion by inducing the expression of SIRT1.     

UCK2 promotes the proliferation,migration, and invasion of trophoblast cells in preeclampsia by activating the STAT3 pathway

Background: Preeclampsia (PE), characterized by hypertension and proteinuria, leads to serious maternal and infant complications. Uridine-cytidine kinase 2 (UCK2) belongs to the UCK family, a class of enzymes that catalyzes the conversion of uridine and cytidine to monophosphate form. However, the role of UCK2 in PE has not been reported. Methods: The expression of UCK2 was detected in the placenta of PE patients and N(ω)-nitro-L-arginine methyl esterinduced PE mouse model. Through forced up-regulation or down-regulation of UCK2 in vitro, we examined the effects of UCK2 on the proliferation, apoptosis, migration, and invasion of trophoblast cells. Stattic, the inhibitor of STAT3 pathway, was used to investigate whether the STAT3 pathway mediates the biological function of UCK2 in trophoblast cells. Results: The present study found that UCK2 showed low expression in the placenta of PE patients and PE mouse model. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and flow cytometry assays verified that up-regulation of UCK2 promoted the proliferation of trophoblast cells, while the silence of UCK2 suppressed cell proliferation. Besides, flow cytometry and TdT-mediated dUTP Nick-End Labeling assays demonstrated that knockdown of UCK2 resulted in apoptosis of trophoblast cells. The wound healing and transwell assays showed that the migration and invasion activities of the trophoblast cells were facilitated by the overexpression of UCK2 and were blocked by the silence of UCK2. Furthermore, the expression of phosphorylated STAT3 was increased with the upregulation of UCK2 and decreased with the inhibition of UCK2. When the STAT3 pathway was blocked by its inhibitor stattic, the promotion effects of UCK2 on trophoblast cells were suppressed. Conclusion: UCK2 promotes the proliferation, migration, and invasion of trophoblast cells, and these effects may be partly mediated by the activation of the STAT3 pathway.     

Effects of polydatin on the proliferation,migration, and invasion of ovarian cancer

To investigate the effects of polydatin on the proliferation, migration, and invasion of ovarian cancer, thechange of proliferative ability, migration ability, and invasive ability of human ovarian cancer cell OVCAR-3, A2780,and HO-8910 was detected by using polydatin and up-regulating PI3K. The anticancer activity and mechanism ofpolydatin in ovarian cancer were analyzed. Polydatin could effectively inhibit the proliferation, migration, and invasionof OVCAR-3, A2780, and HO-8910, and inhibit the expression of PI3K protein. After the expression level of PI3Kprotein was up-regulated, the inhibitory effect of polydatin on the proliferative ability, migration ability, and invasiveability of OVCAR-3, A2780, and HO-8910 significantly decreased, suggesting that PI3K was the target of polydatin.Therefore, we concluded that polydatin could inhibit the proliferation, migration, and invasion of ovarian cancer cellsby inhibiting the expression of PI3K protein, which provides an experimental basis for polydatin in the treatment ofovarian cancer.     

Butyrate inhibits the bovine rumen epithelial cell proliferation via downregulation of positive regulators at G0/G1 phase checkpoint

Short-chain fatty acids (SCFAs) butyrate promote the postnatal rumen epithelial development and maturation in ruminants. However, molecular mechanisms of effects of butyrate on the bovine rumen epithelial cells (BRECs) proliferation remain elusive. Therefore, purpose of this study was to investigate the effects of butyrate on the expression of genes and proteins at G0/G1 and S phase of BRECs cycle. Our results showed that BRECs treated with butyrate inhibited (P < 0.05) the proliferation of BRECs, relatively to control. Flow cytometric assays revealed that butyrate triggers the BRECs cycle arrest at the G0/G1 phase. qRT-PCR analyses of mRNA level of genes involved in the G0/G1 phase of cell cycle showed that butyrate significantly upregulated (P < 0.001) the expression of mRNA encoding p21^Cip1 compared with control group, but it decreased (P < 0.05) the mRNA levels of cyclin D1 and CDK4 genes at G0/G1 phase checkpoint compared with control. Moreover, Western blot also revealed that butyrate downregulated the expression of cyclin D3, CDK6, p-Rb, and E2F1 proteins involved in the modulation of G0/G1 phase of cell cycle. In conclusion, our results demonstrated that butyrate inhibits the proliferation of BRECs via downregulation of positive regulators at G0/G1 phase checkpoint.     

STMN1 promotes the proliferation and inhibits the apoptosis of acute myeloid leukemiacells by activating the PI3K/Akt pathway

Recent studies have shown that the microtubule disrupting protein Stathmin 1 (STMN1) is differentially expressed in AML patients and healthy control. The aim of this study was to explore the effects and molecular mechanism of STMN1 in AML. Here, the expression of STMN1 in peripheral blood cells (PBMCs) and bone marrow of AML patients and healthy volunteers was detected by RT-PCR and Western blot. STMN1 expression was regulated by transfected with STMN1 overexpressed plasmid or shRNA in two human leukemia cell lines K562 and HL60. Cell proliferation was examined by CCK8 and Edu staining. Annexin V and TUNEL assays were applied to test cell apoptosis. Flow cytometry was used to test the cell cycle distribution. The activation of the PI3K signaling pathway and the expression levels of cell cycle and cell apoptosis-related protein were determined by Western blot. In this study, we found that STMN1 was overexpressed in PBMCs and bone marrow of AML patients. STMN1 expression was closely related to FAB subtypes, risk stratification, disease-free survival, and overall survival of AML. Functional assays showed that overexpression of STMN1 in HL60 and K562 cells enhanced cell proliferation, decreased cell apoptosis, and caused G₁ phase arrest. In contrast, suppression of STMN1reduced cell proliferation and enhanced cell apoptosis in both HL60 and K562 cells. Moreover, the PI3K/Akt pathway was activated by STMN1, while suppression of STMN1 dysregulated the PI3K/Akt pathway and upregulating the levels of caspases3 and Bax expression. In conclusion, STMN1 was confirmed to promote the proliferation and inhibit the apoptosis of HL60 and K562 cells by modulating the PI3K/Akt pathway. STMN1 might be a novel molecular target for treating AML.     

Silencing of long non-coding RNA CCHE1 inhibits the ovarian cancer SKOV3 cell invasion and migration and inactivates the p38-MAPK signaling pathway

Ovarian cancer (OC) is a major cause of cancer-related deaths among gynaecological malignancies. Emerging studies suggest that the long non-coding RNA (lncRNA) may be the potential biomarker for the diagnosis and prognosis of the cancer. The current study was carried out to investigate the role of lncRNA CCHE1 silencing in OC cell invasion and migration. Expression of lncRNA CCHE1 in normal ovarian cell Hose and OC cell lines HO 8910, A2780 and SKOV3 was detected. LncRNA were transfected with siRNA, and then the proliferation of cells was detected by using MTT assay. Cell invasion and migration was measured by using Transwell assay and scratch test, respectively. The protein levels of E-cadherin, N-cadherin, ERK, p38-MAPK and the phosphorylation of ERK and p38-MAPK in cells after siRNA transfection were detected by using Western blot analysis. Consequently, lncRNA CCHE1 expression was highly expressed in OC cell lines, especially in SKOV3 cells. siRNA1, siRNA2 and siRNA3 all decreased. lncRNA CCHE1 expression in SKOV3 cells and siRNA2 showed the best silencing efficacy. Silencing of lncRNA CCHE1 decreased proliferation, invasion and migration, and reduced the protein levels of N-cadherin, ERK, p38-MAPK and the phosphorylation of ERK and p38-MAPK, while reducing the protein level of E-cadherin in SKOV3 cells. Collectively, our study proved that the silencing of lncRNA CCHE1 could inhibit SKOV3 cell invasion and migration via inactivating the p38-MAPK signaling pathway.     

Decreased serum HMGB1 associated with M2 macrophage polarization and patients with calcific aortic valve disease

Except for the standard aortic valve replacement, no effective medical treatment is available to prevent or delay calcific aortic valve disease (CAVD) progression. Recently, macrophages and high-mobility group box 1 (HMGB1) are the most intriguing candidates in various inflammatory disorders. However, the association between serum HMGB1, CAVD, and macrophage polarization remains unclear. Therefore, we examined whether the level of serum HMGB1 is clinically associated with aortic valve calcification and whether HMGB1 treatment can promote macrophage differentiation toward M1 or M2 phenotype. This experimental study included 19 CAVD patients and 20 healthy controls whose serum HMGB1 levels were examined by ELISA assay. THP-1 macrophage polarization system was established to test the polarization capability of HMGB1 treatment. The results showed that serum levels of HMGB1 were significantly reduced in patients with CAVD. HMGB1 treatment promoted M2 macrophage polarization but not M1 phenotype with increased IL-10 expression and reduced inducible nitric oxide synthase (iNOS) expression. Our findings suggest that serum HMGB1 is negatively associated with the development of aortic valve calcification, and HMGB1 treatment may facilitate M2 macrophage polarization for reducing aortic valve calcification.     

KIF18A is a potential prognostic factor and promotes tumor progression in oral tongue squamous cell carcinoma

The kinesin family member 18A protein was dysregulated in several human cancers and involved in cancer progression. However, the significance in oral tongue squamous cell carcinoma (OTSCC) has not been studied. The present study was intended to explore the functions of KIF18A in oral tongue squamous cell carcinoma. The immunohistochemistry (IHC) assay was performed to assess the relationships between the KIF18A protein expression level and clinical-pathological features of the patients. The biological functions of KIF18A in OTSCC cells were investigated by the experiments in vitro and in vivo. Based on immunohistochemistry, we found that KIF18A was correlated with the clinical-pathological features of OTSCC patients. High expression of KIF18A was associated with the lymph node metastasis, and clinical stages. In vitro experiments revealed that silencing of KIF18A significantly inhibited the expression of the proliferation and migration related proteins such as Ki67, proliferating cell nuclear antigen, matrix metalloproteinase-7 and matrix metalloproteinase-9, and thereby inhibiting the proliferation, migration and invasion of tumor cells. In vivo, knocking-down of KIF18A could inhibit the tumor growth in nude mice. In conclusion, we found KIF18A promoted tumor progression in vivo and in vitro and might become an effective target for the treatment of OTSCC.     

High level of circPTN promotes proliferation and stemness in gastric cancer

Increasing evidence proves that circular RNAs (circRNAs) play an important role in regulating the biological behaviors of tumors. The central purpose of this research was to investigate the functions of circRNA in gastric cancer. The utilization of real-time PCR was to test circPTN expression in gastric cancer cells. Cell counting colony formation assays, CCK-8 assay, and EdU assay were used to investigate proliferation. Transwell assay was applied to investigate migration. We discovered that circPTN was highly expressed in gastric cancer cells. Low expression of circPTN inhibits gastric cancer cell proliferation and migration. Elevated expression of circPTN promotes gastric cancer cell proliferation and migration. Moreover, we discovered that circPTN could accelerate self-renewal and increase the expression of stemness markers. The results of our study suggested that a high level of circPTN expression promotes the proliferation and stemness of gastric cancer cells.     

MicroRNA-145-3p suppresses the malignant behaviors of T-cell acute lymphoblastic leukemia Jurkat cells via inhibiting the NFkappaB signaling pathway

T-cell acute lymphoblastic leukemia (T-ALL) is a hematological tumor caused by the malignant transformation of immature T-cell progenitor cells. Emerging studies have stated that microRNAs (miRNAs) may play key roles in T-ALL progression. This study aimed to investigate the roles of miR-145-3p in T-ALL cell proliferation, invasion, and apoptosis with the involvement of the nuclear factor-kappaB (NF-κB) signaling pathway. T-ALL Jurkat cells were harvested, and the expression of miR-145-3p and NF-κB-p65 was measured. Gain- and loss-of-functions of miR-145-3p and NF-κB-p65 were performed to identify their roles in the biological behaviors of Jurkat cells, including proliferation, apoptosis, and invasion. Consequently, the current study demonstrated that miR-145-3p was downregulated while NF-κB-p65 was up-regulated in Jurkat cells. miR-145-3p directly bound to the 3’ untranslated region of NF-κB-p65. Over-expression of miR-145-3p inhibited Jurkat cell proliferation, invasion, and resistance to apoptosis, while over-expression of NF-κB-p65 presented opposite trends. Co-transfection of miR-145-3p and NF-κB-p65 promoted the malignant behaviors of Jurkat cells compared to miR-145-3p transfection alone, while it reduced these behaviors of Jurkat cells compared to NF-κB-p65 transfection alone. Taken together, this study provided evidence that miR-145-3p could suppress proliferation, invasion, and resistance to the death of T-ALL cells via inactivating the NF- κB signaling pathway.     

KIFC1 overexpression promotes prostate cancer cell survival and proliferation <i>in vitro</i> by clustering of amplified centrosomes via interaction with Centrin 2

Mitotic kinesin KIFC1 plays critical roles in mitosis by regulating the spindle length, pole formation, and known for clustering extra centrosomes in cancer cells. Centrosome clustering is associated with the survival of cancer cells, but this phenomenon remains obscure in prostate cancer (PCa). The present study demonstrated that PCa cells showed centrosome amplification and clustering during interphase and mitosis, respectively. KIFC1 is highly expressed in PCa cells and tumor tissues of prostatic adenocarcinoma (PAC) patients. Up-regulation of KIFC1 facilitated the PCa cell survival in vitro by ensuring bipolar mitosis through clustering the multiple centrosomes, suggesting centrosome clustering could be a leading cause of prostate carcinogenesis. Conversely, the silencing of KIFC1 resulted in normal centrosome number or multipolar mitosis by inhibiting the clustering of amplified centrosomes in PCa cells. Besides, knockdown of KIFC1 by RNAi in PCa cells reduced cancer cell survival, and proliferation. KIFC1 interacted with centrosome structural protein Centrin 2 in clustering of amplified centrosomes in PCa cells to ensure the bipolar mitotic spindle formation. Knockdown of Centrin 2 in PCa cells inhibited the centrosome amplification and clustering. Moreover, up-regulated KIFC1 promotes PCa cell proliferation via progression of cell cycle possibly through aberrant activation of cyclin dependent kinase 1(Cdk1). Therefore, KIFC1 can be a prognostic marker and therapeutic target of PCa for inhibiting the cancer cell proliferation.     

Interaction of IL-22/IL-22R1 promotes cell proliferation and suppresses apoptosis of colorectal cancer via phosphorylation of STAT3

Interleukin-22 (IL-22) is a member of IL-10 cytokine family which is expressed in activated T cellspredominantly and in activated natural killer cells at lower levels. Previous studies have demonstrated the link betweenelevated levels of IL-22 and disease severity of psoriasis, Crohn’s disease, rheumatoid arthritis and interstitial lungdiseases. However, the function of IL-22 in the development and progression of colorectal cancer (CRC) remainselusive. In this study, we first evaluated the IL-22/IL-22R1 level in CRC patients, and found that tumor tissueshave more active expression of IL-22 and IL-22R1 than normal tissues, presenting correlation with the degree ofdifferentiation of tumor tissues. Subsequently, Caspase and cell viability assays were performed on SW-480 cell linewhich expresses high level of IL-22R1 to examine if the supplementation of IL-22 has an impact on apoptosis andproliferation. In comparison with treatment of 5-FU, supplementation of IL-22 promoted cell proliferation andameliorated apoptosis. To unveil signal transduction upon activation of IL-22R, we examined the phosphorylationof STAT3 in SW-480 cell line following supplementation of IL-22. The treatment of IL-22 also increased the level ofp-Akt, an essential component in PI3K/Akt pathway. Although the link between STAT3 phosphorylation and PI3K/Akt activation remains to be explored, our study revealed the mechanism underlying the effects of IL-22R activation onapoptosis as well as tumor differentiation, indicating the prognostic value of IL-22/IL-22R.     

Electron microscopy of squamous cell carcinoma of the head and neck

Squamous cell carcinoma of the head and neck carries a bad prognosis. In order to achieve cure, the most important thing to attain is local tumour control. The main therapy available is external radiotherapy, which can be supplemented when necessary, with interstitial radiotherapy, chemotherapy and surgery. In this paper we have evaluated specimens, taken before therapy, from 35 patients with squamous cell carcinoma of the head and neck. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analyses were made. With SEM, the parameters analysed were the amount and appearance of microvilli, filaments, and blood vessels. From TEM, scoring was made of the filaments, desmosomes, nuclei, nucleoli, mitochondria, and blood vessels. Scoring of the samples showed a difference between the group with recurrent disease (n = 10, Group 1) and the group with local tumor control (n = 25, Group 2) in regard to both blood vessels and intracellular filaments. No differences of the nuclei, nucleoli, or the mitochondria were observed.     

The effect of the anti‐angiogenic drug sunitinib malate on the vascular architecture of oral squamous cell carcinoma

The effects of anti‐angiogenic therapies in guiding tumor angioarchitecture prompted us to examine the modifications in the vascular network of the oral squamous cell carcinoma (SCC) produced by the multitargeted tyrosine kinase inhibitor sunitinib malate. Twelve Syrian hamsters had their right buccal pouches submitted to tumor induction with dimethylbenzanthracene and carbamide peroxide for 55 days. The animals were then divided into two groups of six animals each; group I was treated with sunitinib malate and group II (control) was remained untreated. After 4 weeks, the hamsters had their vascular networks casted by Mercox^® resin and analyzed by scanning electron microscopy. The qualitative study of the vascular network of the control tumor‐bearing pouches showed images of intussusception and sprouting angiogenesis, flattened blood vessels, abrupt variations in their diameter, and a tortuous course. The samples treated with sunitinib exhibited a qualitative reduction of the signs of vascular proliferation. In addition, these casts presented an attenuation of the morphological features observed in the untreated tumor‐bearing pouches. Quantitative analysis demonstrated that the pouches treated with sunitinib did not show a decrease (P > 0.05) in the vascular diameter and intervessel distances when compared with the control group. The results of the present study suggest that sunitinib may act on the vascular network of oral SCC, normalizing the blood vessels. However, further experiments should be performed in order to determine a judicious dose of this anti‐angiogenic therapy. Microsc. Res. Tech. 77:250–256, 2014. © 2014 Wiley Periodicals, Inc.     

Differential mRNA expression in peripheral blood is associated with oral squamous cell carcinoma: Recent advances and future challenges

Oral squamous cell carcinoma (OSCC) is a malignant tumor triggered by the accumulation of multiple gene mutations in oral epithelial cells. Different OSCC-related biomarkers have been reported in circulation in the peripheral blood that support the occurrence and development of OSCC. Recent advances in high-throughput and highly sensitive detection methods have overcome the limitation of the low concentration of most peripheral blood biomarkers. Hence, blood biomarker detection has become an efficient screening tool for the early diagnosis of OSCC. The growing data available in public cancer and gene databases have provided new foundations for OSCC research. In particular, the identification of OSCC biomarkers using bioinformatic tools has shed new light on the underlying mechanisms as well as on the genetic landscape of OSCC. More recently, mRNA targeting therapies have emerged as valuable anticancer treatment strategies, as they allow for the regulation of the expression of certain functional proteins to reverse genetic abnormalities or induce tissue repair. Thus, mRNA-targeting therapies can be used to regulate the expression of antigens, antibodies, or cellular receptors by immune cells. Particularly, anti-cancer cellular immunotherapy carrying specific mRNAs has attracted significant attention in OSCC treatment. Here, we review the present knowledge on the role of peripheral blood mRNAs in the diagnosis, treatment, development, and prognosis of OSCC. Moreover, we address future research prospects of mRNAs in the peripheral blood in OSCC and the opportunities and challenges that may arise in future clinical therapeutic applications.     

Cobalt chloride stimulates phosphoinositide 3-kinase/Akt signaling through the epidermal growth factor receptor in oral squamous cell carcinoma

Tumor cells are often found under hypoxic conditions due to the rapid outgrowth of their vascular supply, and, in order to survive hypoxia, these cells induce numerous signaling factors. Akt is an important kinase in cell survival, and its activity is regulated by the upstream phosphoinositide 3-kinase (PI3K) and receptor tyrosine kinases (RTKs). In this study, we examined Akt activation and RTKs/PI3K/Akt signaling using the hypoxia-mimetic cobalt chloride in oral squamous carcinoma cells. Cobalt chloride increases Akt phosphorylation in both a dose- and time-dependent manner. Blocking the activation of the PI3K/Akt pathway using LY294002 abolished Akt activation in response to cobalt chloride, suggesting that Akt phosphorylation by cobalt chloride is dependent on PI3K. In addition, activation of the PI3K/Akt pathway seems to rely on the epidermal growth factor receptor (EGFR), since the inhibition of EGFR attenuated cobalt chloride-induced Akt activation. The results in this study also demonstrate that cobalt chloride increases EGFR protein levels and induces oral squamous cell carcinoma cells to enter S phase.     

Intrauterine high androgen promotes obesity of the offspring of rats with polycystic ovarian syndrome via activating macrophage-angiogenesis-related androgen signaling

The development of polycystic ovary syndrome (PCOS) is closely related to the chronic inflammatory and obese. Recent studies have found macrophages regulate the chronic inflammation and adipose tissue remodelling, but the underlying mechanisms have not been clarified. In this study, we established a model of PCOS in the offspring rats by high androgen exposure during late pregnancy in parental and established a female rat macrophage eliminating model by rejection of clodronate liposome. Then, the offspring rat macrophage phenotype in offspring female rat adipose tissue, and levels of testosterone, angiogenic factors (PDGF and VEGF) and inflammatory factors (TNF-α and MCP-1) were investigated. By coculture of RAW264.7 macrophage with adipocytes or C166 endothelial cells (ECs), the mobility of adipocytes, and the ECs function with associated signalling pathway were detected by using of androgen inhibitor Apalutamide, NF-κB inhibitor JSH-23 and ERK1/2 inhibitor LY3214996. It was found that high androgen exposure during late pregnancy led to increased testosterone levels and overweight and obesity, increased size and reduced number of subcutaneous and intra-abdominal adipocytes, and increased secretion of TNF-α and MCP-1 in female rats in the offspring. Eliminating macrophages significantly increased adipocytes and angiogenesis in offspring of rats with intrauterine high androgen, and reduced TNF-α and MCP-1. Macrophages promoted mobility of adipocytes, and inhibited proliferation, migration, tube formation of ECs under hyperandrogenic condition, which were significantly inhibited by Apalutamide, JSH-23 and LY3214996. Thus, intrauterine high androgen promotes obesity of the offspring of rats with polycystic ovarian syndrome through increasing M1 differentiation of pro-inflammatory macrophages and activating VEGF-related angiogenesis via androgen/NF-κB/ERK1/2 signalling pathway.     

Glucocorticoid reduces the efficacy of afatinib on the head and neck squamous cell carcinoma

Glucocorticoids (GC) are widely used to counter the adverse events during cancer therapy; nonetheless, previous studies pointed out that GC may reduce the efficacy of chemotherapy on cancer cells, especially in epidermal growth factor receptor (EGFR)-targeted therapy of head and neck squamous cell carcinoma (HNSCC) remaining to be elucidated. The primary aim of the present study was to probe into the GC-induced resistance of EGFR-targeted drug afatinib and the underlying mechanism. HNSCC cell lines (HSC-3, SCC-25, SCC-9, and H-400) and the human oral keratinocyte (HOK) cell lines were assessed for GC receptor (GR) expression. The promoting tumor growth effect of GC was evaluated by the CCK-8 assay and flow cytometry. Levels of signaling pathways participants GR, mTOR, and EGFR were determined by quantitative polymerase chain reaction and western blotting. GC increased the proliferation of HNSCC cells in a GR-dependent manner and promoted AKT/mTOR signaling. But GC failed in counteracting the inhibition of rapamycin in the mTOR signaling pathway. Besides, GC also induced resistance to EGFR-targeted drug afatinib through AKT/mTOR instead of the EGFR/ERK signaling pathway. Thus, GCs reduce the efficacy of afatinib on HNSCC, implicating a cautious use of glucocorticoids in clinical practice.     

Effect of Peroxiredoxin 1 on the biological function of airway epithelial cells and epithelial-mesenchymal transition

Peroxiredoxin 1 (PRDX1) participates in tumor cell proliferation, apoptosis, migration, invasion, and the epithelial-to-mesenchymal transition (EMT). This study aimed to investigate the effect of PRDX1 on the EMT of airway epithelial cells stimulated with lipopolysaccharide (LPS) and transforming growth factor-beta 1 (TGF-β1). PRDX1 overexpression significantly increased the proliferation and migration of human bronchial epithelial (BEAS-2B) cells, reduced cell apoptosis (p < 0.01), and induced EMT and collagen deposition by upregulating the expression of the matrix metallopeptidase (MMP)2, MMP9, α-smooth muscle actin (α-SMA), N-cadherin, vimentin and twist proteins and inhibiting E-cadherin expression (p < 0.05). PRDX1 overexpression promoted TGF-β1-mediated inhibition of cell proliferation and migration and significantly enhanced the TGF-β1-induced EMT and collagen synthesis (p < 0.05). Knockdown of PRDX1 inhibited cell proliferation, migration, EMT, and collagen synthesis (p < 0.01), reversed LPS-mediated inhibition of cell proliferation and migration, and significantly suppressed LPS-induced EMT and collagen synthesis (p < 0.01). The result indicating that PRDX1 may be involved in LPS/TGF-1-induced EMT and collagen synthesis in human bronchial epithelial cells.