Differential effects of chemotherapeutic agents on the Bcl-2/Bax apoptosis pathway in human breast cancer cell line MCF-7

被引:86
作者
Leung, LK [1 ]
Wang, TTY [1 ]
机构
[1] NCI, Basic Res Lab, Frederick Canc Res & Dev Ctr, NIH, Frederick, MD 21702 USA
关键词
apoptosis; Bax; Bcl-2; breast; chemotherapy; estradiol;
D O I
10.1023/A:1006190802590
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The present study explored the effects of three commonly used chemotherapeutic agents on the Bcl-2/Bax apoptosis pathway and the interaction of these chemotherapeutic drugs with the estradiol-mediated regulation of this pathway. Our results showed that: (1) Treatment of MCF-7 cells with Adriamycin resulted in time- and concentration-dependent decreases in Bcl-2 and increases in Bax mRNA and protein levels. (2) Camptothecin elicited similar trends on Bcl-2 and Bax as Adriamycin, while etoposide, at 50-100 fold (1-5 mu M) the effective concentration of Adriamycin and camptothecin, only resulted in an increase in Bax mRNA levels. (3) Adriamycin and camptothecin, but not etoposide, were effective in suppressing estradiol-stimulated increases in Bcl-2 mRNA levels. Our study provides evidence that the Bcl-2/Bax apoptosis pathway may be differentially regulated by chemotherapeutic agents. In addition, interaction between these agents and estradiol on the Bcl-2/Bax apoptosis pathway may also exist.
引用
收藏
页码:73 / 83
页数:11
相关论文
共 25 条
[1]   The Bcl-2 protein family: Arbiters of cell survival [J].
Adams, JM ;
Cory, S .
SCIENCE, 1998, 281 (5381) :1322-1326
[2]   Regulation of BRCA1 and BRCA2 expression in human breast cancer cells by DNA-damaging agents [J].
Andres, JL ;
Fan, SJ ;
Turkel, GJ ;
Wang, JA ;
Twu, NF ;
Yuan, RQ ;
Lamszus, K ;
Goldberg, ID ;
Rosen, EM .
ONCOGENE, 1998, 16 (17) :2229-2241
[3]   APOPTOSIS AND DISEASE [J].
CARSON, DA ;
RIBEIRO, JM .
LANCET, 1993, 341 (8855) :1251-1254
[4]  
CHABNER BA, 1996, CANC CHEMOTHERAPY
[5]  
FORNARI FA, 1994, CELL GROWTH DIFFER, V5, P723
[6]   Growth arrest and non-apoptotic cell death associated with the suppression of c-myc expression in MCF-7 breast tumor cells following acute exposure to doxorubicin [J].
Fornari, FA ;
Jarvis, WD ;
Grant, S ;
Orr, MS ;
Randolph, JK ;
White, FKH ;
Gewirtz, DA .
BIOCHEMICAL PHARMACOLOGY, 1996, 51 (07) :931-940
[7]   IMMUNOCYTOCHEMICAL LOCALIZATION OF BCL-2 PROTEIN IN HUMAN BREAST CANCERS AND ITS RELATIONSHIP TO A SERIES OF PROGNOSTIC MARKERS AND RESPONSE TO ENDOCRINE THERAPY [J].
GEE, JMW ;
ROBERTSON, JFR ;
ELLIS, IO ;
WILLSHER, P ;
MCCLELLAND, RA ;
HOYLE, HB ;
KYME, SR ;
FINLAY, P ;
BLAMEY, RW ;
NICHOLSON, RI .
INTERNATIONAL JOURNAL OF CANCER, 1994, 59 (05) :619-628
[8]  
Goldwasser F, 1996, ONCOL RES, V8, P317
[9]  
Haldar S, 1996, CANCER RES, V56, P1253
[10]   Activation of CD95 (APO-1/Fas) signaling by ceramide mediates cancer therapy-induced apoptosis [J].
Herr, I ;
Wilhelm, D ;
Bohler, T ;
Angel, P ;
Debatin, KM .
EMBO JOURNAL, 1997, 16 (20) :6200-6208