赛特铂对人卵巢癌细胞A2780的凋亡诱导作用

目的：观察赛特铂对人卵巢癌细胞A2780的凋亡诱导作用及对细胞周期的影响。方法：MTT法观察药物对细胞增殖的抑制作用，碘化丙锭染色分析细胞周期变化，电镜和荧光显微镜观察细胞形态学变化，多参数流式细胞术及TUNEL法检测细胞凋亡率，并测定caspase-3的活性变化及caspase抑制剂对细胞存活率的影响。结果：赛特铂可抑制A2780细胞的增殖并诱导凋亡，具有明显的剂量依赖性，作用与顺铂相当。赛特铂主要导致A2780细胞S期细胞明显增加，G2／M期细胞少许增加。经赛特铂作用后漂浮细胞呈现典型凋亡细胞形态学改变。caspase-3活性随着细胞凋亡率增加而增加，caspase抑制剂不完全抑制细胞死亡。结论：赛特铂影响A2780细胞周期分布，可体外诱导A2780细胞凋亡。caspase依赖性和caspase非依赖性途径参与了其凋亡过程，其中caspase依赖性途径又包括caspase-3依赖性和非easpase-3依赖性途径。

Apoptosis induced by satraplatin in human ovarian carcinoma cells A2780

AIM: To observe the growthinhibiting cell cycle-modifying and apoptosis-inducing effects of satraplatin on human ovarian carcinoma cell line A2780, and to explore its possible mechanism. METHODS: The effect of satraplatin on A2780 cells proliferation was determined using MTT, and the change in cell cycle was analyzed using PI staining. Morphologic change was visualized by fluorescence and electron microscopy. AnnexinV-FITC/PI staining multiparameter flow cytometry and immuno- histochemical TUNEL assay were used to detect apoptotic cells. The activity of caspase-3 and the effect of pan-caspase inhibitor on cell viability were measured as well. RESULTS: The growthinhibiting and apoptosis-inducing effects of satraplatin were dose-dependent and similar to those of cisplatin. Satraplatin mainly caused A2780 cell accumulation in S phase accompanied by minor accumulation in G2/M phase. Cells treated with satraplatin exhibited typical morphology of apoptosis. Satraplatin-induced increase in caspase-3 activity of A2780 cells was concentration-dependent. The viability of A2780 cells was affected by pan-caspase inhibitor z-VAD-fmk in a dose-dependent manner under certain concentration of z-VAD-fmk. CONCLUSION: Satraplatin-induced apoptosis in A2780 in vitro was observed. Caspase-dependent and independent pathways were involved in apoptosis induced by satraplatin, and the latter included caspase-3 dependent and non-caspase-3 dependent pathways.