雷帕霉素联合多西紫杉醇对肺癌细胞增殖和凋亡的影响

摘要

Objective To study the effects of rapamycin ( RAPA) which inhibition of mammalian target of RAPA (mTOR) combined with docetaxel(DOC) on proliferation and apoptosis of lung cancer cell lines A549,SPC-A-1,95D and NCI-H446. Methods The effect on the proliferation of lung cancer cells in different concentration RAPA group, DOC group and DOC combined with 20.0 nmol ? L-1 RAPA group were evaluated using methyl thiazolyl tetrazolium( MTT) method,and 95D lung cancer cell apoptosis in three groups were measured by flow cytometry. Results RAPA could inhibit the lung cancer cell proliferation and its role in a dose-dependent fashion. DOC alone and DOC combined with 20. 0 nmol ? L-1 RAPA could inhibit the lung cancer cell proliferation, and inhibition rate of combined application significantly increased ( P < 0.05 ). Flow cytometry shown that RAPA and DOC could increase the apoptosis ratio of 95 D lung cancer cell ( P < 0.05), and inhibition rate of combined application significantly increased (P < 0.05). Conclusion mTOR pathway may be involved in proliferation and apoptosis of lung cancer cells. Inhibition of mTOR,RAPA can enhance the anti-tumor effect of DOC.%目的 探讨哺乳动物雷帕霉素靶蛋白( mTOR)信号通路抑制剂雷帕霉素(RAPA)联合多西紫杉醇(DOC)对肺癌细胞系A549、SPC-A-1、95D和NCI-H446增殖抑制及凋亡的影响.方法 甲基噻唑基四唑(MTT)法检测不同浓度RAPA组、DOC组及DOC联合20.0 nmol·L-RAPA组对肺癌细胞系增殖抑制作用；流式细胞仪法检测RAPA组、DOC组及DOC联合20.0 nmol·L-1 RAPA组对肺癌95D细胞凋亡的影响.结果 RAPA能抑制肺癌细胞的增殖,其作用呈剂量依赖性；单独应用DOC及DOC联合20.0 nmol·L-1 RAPA均可显著抑制肺癌细胞的增殖,且联合应用抑制率显著升高(P＜0.05)；流式细胞仪检测显示RAPA及DOC均可增加肺癌95D细胞的凋亡率(P＜0.05),联合应用明显增加细胞的凋亡率(P＜0.05).结论 mTOR信号通路参与肺癌细胞的增殖与凋亡,mTOR信号通路抑制剂RAPA可增强DOC的抗肿瘤效应.