The p21(cip1/waf1) cyclin-dependent kinase inhibitor enhances the cytotoxic effect of cisplatin in human ovarian carcinoma cells

The seriousness of ovarian cancer, which is related to the observed link be tween recurrency and cell cycle control defect, prompted us to explore the effect of ectopic expression of the cdk inhibitor p21(cip1/waf1) on ovarian carcinoma chemosensitivity. The transfection of p21(cip1/waf1) cDNA into S KOV3 and OVCAR3 cells led to reduction of tumor cell growth, enhanced susce ptibility to cisplatin-induced apoptosis, and abolition of recurrency after cisplatin exposure. p21(cip1/waf1) gene transfer allowed a marked reductio n of the cisplatin concentration needed to erradicate the tumor cell popula tion. These results suggest exploring the possible use of p21(cip1/waf1) as an adjunctive to conventional chemotherapy. (C) 2000 Elsevier Science Irel and Ltd, All rights reserved.