Differential Effects of Chemotherapeutic Agents on the Bcl-2/Bax Apoptosis Pathway in Human Breast Cancer Cell Line MCF-7

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 microM) 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.