122eP Preclinical investigation of the potential synergistic action of small molecule inhibitors in combination with chemotherapy in colon and liver cancer cells

tumorigenic Balb 3T3 and tumorigenic 3T3-B61 cells (derived from Balb 3T3 fibroblasts, transfected in our laboratory with constitutively expressed H-Ras-V12 oncoprotein) were analyzed using XTT viability, clonogenic, growth curve, and Western blot assays.For in vivo studies, 110 6 3T3-B61 cells were injected subcutaneously into BALB/c mice. Results:The FGF-2+Bortezomib combination showed synergistic cytotoxicity in 3T3-B61 cells, but not in Balb 3T3.Growth and clonogenic assays confirmed tumorigenic cell sensitivity and non-tumorigenic cell recovery.MAPK activation occurred in both cell lines, yet increased BIP expression in 3T3-B61 indicated proteotoxic stress and UPR dysregulation, correlating with Bortezomib sensitivity.Conversely, LB100+Bortezomib induced cytotoxicity in both cell types, indicating a narrower therapeutic window.In vivo, FGF-2+Bortezomib significantly reduced tumor volume compared with controls.Conclusions: FGF-2+Bortezomib enhances cytotoxicity selectively in tumor cells, whereas LB100+Bortezomib affects both.These findings support the concept that combining mitogenic activation with stress-response inhibition represents an unconventional but promising therapeutic strategy for cancer treatment.