[关键词]
[摘要]
目的:研究雷帕霉素 (rapamycin) 对胆囊癌GBCSD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pmTOR水平。结果:雷帕霉素可显著抑制胆囊癌GBCSD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<001)。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pmTOR通路、诱导细胞周期阻滞和细胞凋亡有关。
[Key word]
[Abstract]
Objective:To investigate the effect of rapamycin on cell growth and migration of gallbladder cancer GBCSD cells, and to discuss its potential in clinical therapy of gallbladder cancer. :Methods: :Proliferation of GBCSD 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 GBCSD cells treated with different concentrations of rapamycin were determined by flow cytometry. Migration ability of GBCSD cells was assessed by Transwell assay. The expression of mTOR (mammalian target of rapamycin) and its phosphorylation in GBCSD 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 GBCSD cells. Rapamycin significantly inhibited the growth of GBCSD cells in a dosedependent manner (P<0.01). Rapamycin induced apoptosis of GBCSD cells and arrested them at the G1/S phase. Furthermore, rapamycin also significantly suppressed migration of GBCSD 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 pmTOR pathway, induction of apoptosis and cell cycle arrest of gallbladder cancer cells.
[中图分类号]
[基金项目]