研究mTOR抑制剂依维莫司在体外对人前列腺癌PC-3细胞株的作用及其机制.docVIP

精品论文 参考文献 研究mTOR抑制剂依维莫司在体外对人前列腺癌PC-3细胞株的作用及其机制 陕西延安人民医院 716000 摘要：目的：体外研究mTOR抑制剂依维莫司（Everolimus，RAD001）对人前列腺癌PC-3细胞株增殖的改变，并探讨其可能的作用机制。方法：体外采用细胞培养技术培养人前列腺癌PC-3细胞株，MTT法检测依维莫司1nmol/L对PC-3细胞株增殖的变化；流式细胞分析技术（FCM）检测维莫司对PC-3细胞株细胞周期的变化；Western blot检测依维莫司干预PC-3细胞株后，p-4E-BP1和p-P70-S6K表达情况的改变。采用SPSS13.0统计软件对实验所得数据分析，P＜0.05有统计学差异。结果：MTT结果显示，依维莫司可抑制PC-3细胞株的增殖，且随着药物干预时间的延长，抑制率逐步增大（Plt;0.01）；FCM结果显示，随着药物干预时间的延长，G0/G1期的细胞百分比逐步升高，S、G2/M期的细胞百分比逐步降低，使绝大部分PC-3细胞被中断在细胞周期的G0/G1期（P ＜0.01）；Western blot结果显示，随着药物干预时间的延长，p-4E-BP1和p-P70-S6K的表达逐步被抑制（Plt;0.01）。结论：mTOR抑制剂依维莫司能够抑制人前列腺癌PC-3细胞株的增殖，其机制可能与PI3K/Akt/mTOR信号传导通路中的mTOR被抑制，继而抑制了其下游的翻译抑制因子eIF-4E结合蛋白1（4E-BP1）和核糖体蛋白P70-S6K的磷酸化有关。 关键词：依维莫司（Everolimus，RAD001）；mTOR；前列腺癌；PC-3细胞株；增殖 [ABSTRACT]Objective：To research of changes of mTOR inhibitors Everolimus（RAD001）on proliferation of human prostate cancer PC-3 cell lines in vitro，and search for its possible mechanism.Methods：Human prostate cancer PC-3 cell lines were cultivated in vitro by Cell culture technology and then interfered with by 1nmol/l Everolimus.Changes of Everolimus on the proliferation of PC-3 cell lines was detected by MTT assay；The influence of Everolimus on the cell cycle change was detected by Flow cytometry analysis（FCM）；The changes of Everolimus on expression of p-4E-BP1 and p-P70-S6K was detected by Western blot analysis.Experimental dates were analyzed by SPSS 13.0，and Plt;0.05 is defined as a Statistically significant difference.Results：MTT assays results suggested that Everolimus can inhibit the proliferation of PC-3 cell lines，and with the extension of drug intervention time，the inhibition rate rise gradually（Plt;0.01）；The results of Flow cytometry analysis（FCM）revealed that，with the extension of drug intervention time，the cell proportion of G0/G1 phase rises gradually，the cell proportion of S，G2/M phase decline gradually，and make the most of the PC-3 cells are interrupted in G0/G1 phase of the cell cycle（Plt;0.01）；Western blot analysis showed that，with the extension of dru