Combination effect of adenovirus-mediated ppo-apoptotic bax gene transfer with cisplatin or paclitaxel treatment in ovarian cancer cell lines

To develop a novel therapeutic strategy for ovarian cancer, we constructed a recombinant adenovirus which highly expresses pro-apoptotic Bax protein a nd examined its therapeutic effect on a series of ovarian cancer cell lines : A2780, A2780/cDDP, OVCAR-3 and SK-OV-3. A recombinant adenovirus carrying the Bax-alpha gene (AxCALNKYbax) induced high expression of the Bar-alpha protein in all the cell lines. The cytotoxic effect of Bar was observed in three ovarian cancer cell lines: the per cent reduction in the number of ce lls was 40.0% for cisplatin-sensitive A2780, 50.0% for cisplatin-resistant A2780/cDDP, and 64.8% for marginally cisplatin-resistant OVCAR-3. In contra st, it was only 12.3% for cisplatin-resistant SK-OV-3. Cisplatin-resistant A2780/cDDP had a p53 mutation and exhibited attenuated Bar induction after cisplatin treatment, which may explain why supplementation of Bar was effec tive in this chemoresistant ovarian cancer. Combination with cisplatin or p aclitaxel enhanced the cytotoxic effect of Bar induction in all but one cel l line including cisplatin-resistant A2780/cDDP. It appears that adenovirus -mediated Bar induction, with or without combination with conventional chem otherapy, useful strategy for the treatment of ovarian cancer. (C) 2001 Els evier Science Ltd. All rights reserved.