The p21cip1/waf1 cyclin-dependent kinase inhibitor enhances the cytotoxic effect of cisplatin in human ovarian carcinoma cells

被引:95
作者
Lincet, H
Poulain, L
Remy, JS
Deslandes, E
Duigou, F
Gauduchon, P
Staedel, C
机构
[1] Ctr Reg Lutte Canc Francois Baclesse, Expt Cancerol Lab, INSERM, CJF 96 03, F-14076 Caen 05, France
[2] Ctr Reg Lutte Canc Francois Baclesse, Expt Cancerol Lab, INSERM, EA 1772, F-14076 Caen, France
[3] Fac Pharm Strasbourg, Lab Chim Genet, CNRS, UMR 7514, F-67401 Illkirch, France
[4] Ctr Francois Baclesse, Anat Pathol Lab, F-14076 Caen 05, France
关键词
ovarian carcinoma; cdk-inhibitor p21(cip1); cisplatin; chemoresistance; apoptosis;
D O I
10.1016/S0304-3835(00)00586-3
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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. (C) 2000 Elsevier Science Ireland Ltd, All rights reserved.
引用
收藏
页码:17 / 26
页数:10
相关论文
共 41 条
[1]  
Auersperg N, 1998, SEMIN ONCOL, V25, P281
[2]   EXPRESSION OF P21(WAF1/CIP1) IS HETEROGENEOUS AND UNRELATED TO PROLIFERATION INDEX IN HUMAN OVARIAN-CARCINOMA [J].
BARBOULE, N ;
MAZARS, P ;
BALDIN, V ;
VIDAL, S ;
JOZAN, S ;
MARTEL, P ;
VALETTE, A .
INTERNATIONAL JOURNAL OF CANCER, 1995, 63 (05) :611-615
[3]   p21 binding to PCNA causes G1 and G2 cell cycle arrest in p53-deficient cells [J].
Cayrol, C ;
Knibiehler, M ;
Ducommun, B .
ONCOGENE, 1998, 16 (03) :311-320
[4]  
CHEN YQ, 1995, CANCER RES, V55, P4536
[5]  
DESHANE J, 1994, GENE THER, V1, P332
[6]   P53-DEPENDENT INHIBITION OF CYCLIN-DEPENDENT KINASE-ACTIVITIES IN HUMAN FIBROBLASTS DURING RADIATION-INDUCED G1 ARREST [J].
DULIC, V ;
KAUFMANN, WK ;
WILSON, SJ ;
TLSTY, TD ;
LEES, E ;
HARPER, JW ;
ELLEDGE, SJ ;
REED, SI .
CELL, 1994, 76 (06) :1013-1023
[7]  
ELBENDARY A, 1994, CELL GROWTH DIFFER, V5, P1301
[8]  
ELDEIRY WS, 1994, CANCER RES, V54, P1169
[9]  
Gorospe M, 1996, MOL CELL BIOL, V16, P6654
[10]   p21(Waf1/Cip1) protects against p53-mediated apoptosis of human melanoma cells [J].
Gorospe, M ;
Cirielli, C ;
Wang, XT ;
Seth, P ;
Capogrossi, MC ;
Holbrook, NJ .
ONCOGENE, 1997, 14 (08) :929-935