双氢青蒿素对前列腺癌PC-3细胞生长及Survivin表达的影响

目的观察双氢青蒿素(DHA)对前列腺癌PC-3细胞生长及Survivin表达的影响,并探讨其作用机制。方法PC-3细胞经不同浓度的DHA处理后,MTT法检测细胞增殖抑制率;将PC-3细胞注入裸鼠右侧腋窝下,建立裸鼠种植瘤模型,将20只模型鼠随机分为空白对照组、DMSO对照组、DHA高剂量组(200μmol/kg体重)和低剂量组(100μmol/kg体重),经13d干预后,计算抑瘤率;光镜及电镜观察肿瘤组织形态学改变,免疫组织化学法检测Survivin的表达,TUNEL法检测细胞凋亡。结果DHA可显著抑制PC-3细胞的增殖,并具有时间、浓度依赖性;DHA对裸鼠种植瘤生长具有明显的抑制作用,抑瘤率达60%以上;光镜及电镜观察到DHA两剂量组肿瘤组织中散在凋亡细胞及凋亡小体;DHA两剂量组细胞Survivin表达减弱,凋亡率明显升高。结论DHA可明显抑制PC-3细胞生长,其机制与下调Survivin的表达并诱导肿瘤细胞凋亡有关。

Effect of Dihydroartemisinin on Growth of Prostate Cancer PC-3 Cells and Expression of Survivin

Objective To observe the effect of dihydroartemisinin(DHA)on the growth of prostate cancer PC-3 cells and the expression of survivin.Methods PC-3 cells were treated with DHA at various concentrations and determined for proliferation in-hibiting rate by MTT method.Nude mouse model of transplanted prostate cancer was established by injecting s.c.PC-3 cells into right axillary fossa.Twenty model nude mice were divided into blank control,DMSO control,test 1 and test 2 groups.The mice in test 1 and test 2 groups were injected i.p.with DHA at dosages of 200 and 100 μmol /kg body weight every other day respectively,and those in DMSO control group with DMSO at a dosage of 1 ml /kg body weight,while those in blank control group was untreated.Kill the mice on day 13 after treatment to observe the tumor growth and calculate the tumor inhibiting rate.The morphological change of tumor was observed by light and electron microscopy.The expression of survivin was determined by immunohistochemical assay,and the apoptosis of tumor cells by TUNEL method.Results DHA showed significantly time-and dosage-dependent inhibitory effect on the proliferation of PC-3 cells.The inhibition rate of transplanted tumors in nude mice treated with DHA was more than 60%.Scattered apoptotic cells and apoptotic bodies were observed in the tumor tissues of mice in 2 test groups by both light and electron microscopy.Compared with those in blank control and DMSO control groups,the expression level of survivin in 2 test groups de-creased,while tumor cell apoptosis rate increased significantly.Conclusion DHA inhibited the growth of PC-3 cells significantly by a mechanism of down-regulating the expression of survivin and inducing the apoptosis of tumor cells.