Basic fibroblast growth factor sensitizes NIH 3T3 cells to apoptosis induced by cisplatin

One mechanism by which chemotherapeutic agents kill tumor cells is by induc tion of apoptosis. Basic fibroblast growth factor (bFGF/FGF-2) has been rep orted to inhibit apoptosis in NIH 3T3 cells treated with chemotherapy drugs . We have investigated how bFGF modulates apoptosis induced by cisplatin in NIH 3T3 cells. Treatment with 10 mg/ml cisplatin for 12 h induced apoptosi s in 2 to 13% of the cells at 24 h post-treatment. Preincubation with 10 ng /ml bFGF for 24 h led to cisplatin-induced apoptosis in 20% to 50% of the c ells. Preincubation with lower concentrations of bFGF (0.1-1 ng/ml) or simu ltaneous addition of bFGF and cisplatin had no effect on the amount of apop tosis. Pretreatment with bFGF also significantly decreased the dose-depende nt survival of NIH 3T3 cells exposed to cisplatin, as determined by colony formation. Cells treated with 10 ng/ml bFGF showed a distinct morphology, a ppearing smaller and more refractile, before cisplatin exposure. The enhanc ement of cisplatin-induced apoptosis and the morphology shift demonstrated the same dose response to bFGF, and both effects were reversible if bFGF wa s removed from the medium for 24 h before cisplatin treatment. Mitogenic re sponse to bFGF by NIH 3T3 cells saturated at 0.5 ng/ml, as measured by H-3- thymidine uptake, and this response was blocked by coaddition of suramin, a n inhibitor of FGF ligand-receptor interactions. Suramin did not reverse th e enhancement of cisplatin-induced apoptosis by bFGF. Therefore, bFGF sensi tized NIH 3T3 cells to cisplatin, and this effect might be mediated through a pathway separate from that used for mitogenic signaling.