Basic fibroblast growth factor potentiates cisplatinum-induced cytotoxicity in MCF-7 human breast cancer cells

Basic fibroblast growth factor (bFGF) is a classical mitogen in fibroblasts and endothelial cells. Our previous studies have demonstrated that bFGF in hibits the growth of MCF-7 human breast cancer cells. The aim of the presen t study was to examine the effect of bFGF on cis-diamminedichloroplatinum(c isplatin)induced cytotoxicity in MCF-7 breast cancer cells as compared to n ormal endothelial cells. MCF-7/NCF cells transduced with a vector expressin g the bFGF gene and overexpressing its product, and MCF-7/N2 cells transduc ed with the backbone vector were incubated with a combination of bFGF and c isplatin for 5 days; results were compared with those obtained with bovine aortic endothelial cells. Cell proliferation was assessed with the sulforho damine B colorimetric cytotoxicity assay. Apoptosis was quantitatively dete rmined by flow-cytometric analysis for DNA damage and the apoptotic death a ssay for DNA fragmentation, and qualitatively by electron microscopy. Rever se transcriptase/polymerase chain reaction analysis and an enzyme immunoass ay were used to determine the mRNA and protein level, respectively, of the anti-apoptotic bcl-2 gene product. We found that bFGF enhanced cisplatin-in duced cytotoxicity in MCF-7 breast cancer sublines. bFGF enhanced prolifera tion of normal endothelial cells and did not increase cisplatin-induced cyt otoxicity. This effect was accompanied by down-regulation of the anti-apopt otic protooncogene bcl-2 and the enhancement of cisplatin-induced apoptosis . We suggest that the improved understanding of the role of bFGF in the dif ferential modulation of the response of breast cancer and normal endothelia l cells to chemotherapy may enable active intervention to alter the therape utic ratio favorably in breast cancer patients.