【摘要】 目的:研究雷帕霉素(rapamycin)对胆囊癌GBC-SD细胞生长和转移的影响,探讨雷帕霉素治疗胆囊癌的临床应用前景。方法:采用MTT法检测不同浓度(12.5、25、50 nmol/L)的雷帕霉素对胆囊癌细胞增殖的影响,以流式细胞术检测不同浓度的雷帕霉素对细胞凋亡和细胞周期的变化,Transwell小室检测雷帕霉素对细胞迁移能力的影响,利用Western blotting检测胆囊癌细胞中雷帕霉素哺乳动物靶标(mammalian target of rapamycin,mTOR)及其磷酸化p-mTOR水平。结果:雷帕霉素可显著抑制胆囊癌GBC-SD细胞中mTOR的磷酸化,但对mTOR表达无影响。雷帕霉素显著抑制胆囊癌细胞的生长,并呈剂量依赖性抑制(P<0.01)。雷帕霉素可引起胆囊癌细胞周期G1/S阻滞和细胞凋亡;可显著抑制胆囊癌细胞的转移(P<0.01)。结论:雷帕霉素能显著抑制胆囊癌细胞生长及转移,其机制可能与抑制p-mTOR通路、诱导细胞周期阻滞和细胞凋亡有关。更多还原

【Abstract】 Objective:To investigate the effect of rapamycin on cell growth and migration of gallbladder cancer GBC-SD cells,and to discuss its potential in clinical therapy of gallbladder cancer.Methods: Proliferation of GBC-SD cells treated with different concentrations of rapamycin(12.5,25,and 50 mmol/L)was examined by MTT assay.Cell cycle distribution and apoptosis of GBC-SD cells treated with different concentrations of rapamycin were determined by flow cytometry.Migration ability of GBC-SD cells was assessed by Transwell assay.The expression of mTOR(mammalian target of rapamycin) and its phosphorylation in GBC-SD cells were examined by Western blotting assay.Results: Rapamycin significantly inhibited the phosphorylation of mTOR,but had no influence on the expression of mTOR in GBC-SD cells.Rapamycin significantly inhibited the growth of GBC-SD cells in a dose-dependent manner(P<0.01).Rapamycin induced apoptosis of GBC-SD cells and arrested them at the G1/S phase.Furthermore,rapamycin also significantly suppressed migration of GBC-SD cells as showed by Transwell assay(P<0.01).Conclusion: Rapamycin can remarkably inhibit the growth and migration of gallbladder cancer cells,probably by inhibition of p-mTOR pathway,induction of apoptosis and cell cycle arrest of gallbladder cancer cells.更多还原