Background & objective: Cisplatin-based chemotherapy is an important way for treatment of ovarian cancer, but resistance to cisplatin is one of the reasons of treatment failure of ovarian cancer. This study was designed to investigate the relationship between apoptosis-associated proteins and caspase-3 activity as well as their effects on chemoresistance in human ovarian cancer cell lines.
Methods: The expression of apoptosis-associated proteins (bcl-2, bcl-xL, bax, bcl-xs), the activity of caspase-3 and cleavage of poly ADP-ribose polymerase (PARP) were determined with Western blot analysis in the cisplatin-resistant cell (COC1/DDP) and cisplatin-sensitive human ovarian cancer cell (COC1). The apoptotic ratios of COC1 and COC1/DDP were measured with flow cytometry after treated with different concentration of cisplatin.
Results: The expression of bcl-2 and bcl-XL in COC1/DDP cell was significantly higher than that in COC1 cell, whereas the expression of bax showed no change in COC1/DDP and COC1. There was no bcl-xs expression in both COC1 and COC1/DDP cells. The activity of caspase-3, the amount of PARP fragments, and apoptotic ratio in COC1/DDP reduced much more than COC1 did after treated with cisplatin.
Conclusions: Cisplatin-resistance in human ovarian cancer cell lines may associated with the overexpression of anti-apoptotic protein bcl-2 and downregulation of caspase-3 activity, but not associated with the expression of bax and bcl-xs.