Proteasome Inhibitors Interrupt the Activation of Non-Canonical NF-κB Signaling Pathway and Induce Cell Apoptosis in Cytarabine-Resistant HL60 Cells |
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Authors: | Shuo-Yu Wang Yin-Hwa Shih Tzong-Ming Shieh Yu-Hsin Tseng |
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Affiliation: | 1.Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan;2.Department of Pediatrics, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;3.Department of Healthcare Administration, Asia University, Taichung 41354, Taiwan;4.School of Dentistry, China Medical University, Taichung 40402, Taiwan;5.Department of Dental Hygiene, China Medical University, Taichung 40402, Taiwan |
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Abstract: | Over half of older patients with acute myeloid leukemia (AML) do not respond to cytotoxic chemotherapy, and most responders relapse because of drug resistance. Cytarabine is the main drug used for the treatment of AML. Intensive treatment with high-dose cytarabine can increase the overall survival rate and reduce the relapse rate, but it also increases the likelihood of drug-related side effects. To optimize cytarabine treatment, understanding the mechanism underlying cytarabine resistance in leukemia is necessary. In this study, the gene expression profiles of parental HL60 cells and cytarabine-resistant HL60 (R-HL60) cells were compared through gene expression arrays. Then, the differential gene expression between parental HL60 and R-HL60 cells was measured using KEGG software. The expression of numerous genes associated with the nuclear factor κB (NF-κB) signaling pathway changed during the development of cytarabine resistance. Proteasome inhibitors inhibited the activity of non-canonical NF-κB signaling pathway and induced the apoptosis of R-HL60 cells. The study results support the application and possible mechanism of proteasome inhibitors in patients with relapsed or refractory leukemia. |
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Keywords: | proteasome inhibitors, cytarabine-resistant HL60, NF-κ B, leukemia |
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