[Apoptosis induced by cisplatin and verapamil or SDZ PSC 833 in human ovarian cell lines].

OBJECTIVE

To study the pharmaceutical mechanisms of cisplatin (DDP), verapamil (VP) and SDZ PSC833, and the mechanism of developing acquired drug resistance.

METHODS

Two ovarian carcinoma cell lines--one sensitive (COC(1)) and the other resistant (COC(1)/DDP) to cisplatin were used in this study. The cell viability was measured by trypan blue dye exclusion assay. The apoptotic cells were observed and distinguished by light and electron microscopy, and comet assay. Flow cytometry was used to measure the cell cycle. Six groups were set up according to drug(s) delivered: DDP, VP, SDZ PSC833, DDP and VP, DDP and SDZ PSC833, and control group.

RESULTS

(1) VP or SDZ PSC833 enhanced cytotoxicity of DDP (q > 1, P < 0.01). (2) The most prominent effect of DDP on cell cycle kinetics was a slowdown in S-phase transit during which cells undergo apoptosis (P < 0.05). (3) COC(1) and COC(1)/DDP cells had different rates of apoptosis when DDP added. SDZ PSC833 enhanced apoptosis of COC(1)/DDP cells induced by DDP.

CONCLUSIONS

VP and SDZ PSC833 increase sensitivity of the cell lines to DDP. SDZ PSC833 enhances apoptosis induced by DDP. Induction of apoptosis is one of the pharmaceutical mechanisms of DDP, and acquired drug resistance is associated with resistance to apoptosis. The most prominent effect of DDP on cell cycle kinetics is a slowdown in S-phase transit and apoptotic cells are at S-phase.