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 between 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 SKOV3 and OVCAR3 cells led to reduction of tumor cell growth, enhanced susceptibility to cisplatin-induced apoptosis, and abolition of recurrency after cisplatin exposure. p21(cip1/waf1) gene transfer allowed a marked reduction of the cisplatin concentration needed to erradicate the tumor cell population. These results suggest exploring the possible use of p21(cip1/waf1) as an adjunctive to conventional chemotherapy.
Lincet
H
H
INSERM CJF 96-03 and UPRES-EA 1772, Laboratoire de Cancérologie Experimentale, Centre Régional de Lutte Contre le Cancer François Baclesse, route de Lion-sur-mer, 14076 Cedex 05, Caen, France.
Poulain
L
L
Remy
J S
JS
Deslandes
E
E
Duigou
F
F
Gauduchon
P
P
Staedel
C
C
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000628:therapy*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002945:Cisplatin / Q000494:pharmacology*; D003131:Combined Modality Therapy; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000628:therapy*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D002945:Cisplatin