Apoptosis induced by satraplatin in human ovarian carcinoma cells A2780 / 中国临床药理学与治疗学

ABSTRACT

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.