唑来膦酸对肺癌95D细胞周期阻滞和诱导凋亡的作用机制

目的 研究唑来膦酸对肺癌95D细胞的细胞周期阻滞及诱导凋亡作用.方法 采用二苯基溴化四氮唑蓝法检测唑来膦酸对肺癌95D细胞增殖的影响;采用流式细胞仪检测唑来瞵酸作用后肺癌95D细胞的细胞周期和凋亡的变化,并在光镜和电镜下观察细胞凋亡的形态变化;采用Western blot和逆转录聚合酶链反应检测唑来膦酸对肺癌95D细胞凋亡相关基因ERK1/ERK2、bcl-2、bax和survivin表达水平的影响.结果 唑来膦酸对肺癌95D细胞的增殖抑制作用呈时间和浓度依赖性,94.0% μmol/L唑来膦酸作用6 d时,抑制率达89.8%.随着唑来膦酸作用时间的延长,G1期细胞数量增多,G2期和S期细胞减少,凋亡细胞的数最逐渐增多.光镜和电镜均观察到细胞出现了相应的凋亡形态学变化.细胞凋亡相关基因ERK、bcl-2和survivin的表达水平下降,bax的表达水平增高.结论 唑来膦酸对肺癌95D细胞的细胞周期有阻滞作用,并能诱导其凋亡.

Zoledronic acid blocks cell cycle and induces apoptosis in lung cancer cell line 95D cells and their mechanisms of action

Objective To study the effect of zoledronic acid on cell cycle blocking and induction of apoptosis in lung cancer cell line 95D cells, and their mechanisms of action. Methods The effect of zoledronic acid (ZOL) on proliferation of lung cancer cell line 95D cells was observed by MTT assay. Cell cycle and apoptosis of the lung cancer cells was examined by flow cytometry. The apoptosis in the cancer cells was also examined by light and transmission electron microscopy. The expressions of ERK, Bcl-2, Bax and survivin were measured by Western blot and RT-PCR. Results ZOL showed inhibitory effect on the proliferation of lung cancer cells in vitro, in a time-dependant and a dose-dependant manner. With time extending after ZOL treatment, the number of apoptosis cells was increased. The expression of ERK, Bcl-2 and survivin was down-regulated and that of Bax up-regulated. Conclusion Zoledronic acid can block the cell cycle and induce apoptosis in lung cancer cells in vitro.