Cooperative effect of adenoviral p53 gene therapy and standard chemotherapy in ovarian cancer cells independent of the endogenous p53 status.
Clinical adenoviral p53 gene therapy has been shown by us and others to inhibit tumor growth of ovarian cancer with endogenous mutant p53. This study was designed to test the cooperative antitumor effect of standard combination chemotherapy using paclitaxel and carboplatin together with adenoviral p53 gene transfer in the presence of wild-type and mutant p53. Seven ovarian cancer cell lines with mutant p53 and seven ovarian cancer cell lines with wild-type p53 were tested. An E1-deleted adenovirus type 5 expressing p53 (ACNp53) was used for p53 gene transfer. p53 gene transfer at 50% transduction efficiency significantly reduced IC50 of carboplatin chemotherapy up to 49-fold, of paclitaxel chemotherapy up to six-fold, and of paclitaxel/carboplatin chemotherapy up to 19-fold in the wild-type p53 cell line OV-MZ-5. Synergism between ACNp53 and chemotherapy calculated by median-effect analysis was found at low drug concentrations in all cell lines independent of the p53 mutational status. In conclusion, adenoviral p53 gene transfer significantly increased the sensitivity of ovarian tumor cells to paclitaxel, to carboplatin and/or to the combination of both.
Quist
Sven R
SR
Department of Obstetrics & Gynecology, University of Ulm, Prittwitzstrasse 43, D-89075, Germany.
Wang-Gohrke
Shan
S
Köhler
Tanja
T
Kreienberg
Rolf
R
Runnebaum
Ingo B
IB
D000256:Adenoviridae / Q000235:genetics*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis; D016190:Carboplatin / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D016158:Genes, p53; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D020128:Inhibitory Concentration 50; D009154:Mutation / Q000235:genetics; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000628:therapy*; D017239:Paclitaxel / Q000627:therapeutic use; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D016159:Tumor Suppressor Protein p53; D016190:Carboplatin; D017239:Paclitaxel