Bortezomib therapeutic effect is associated with expression of FGFR3 in multiple myeloma cells

The ectopically expressed and deregulated fibroblast growth factor receptor 3 (FGFR3) has been observed in ∼20% of multiple myeloma (MM) patients. In this study, we investigated whether the therapeutic effect of bortezomib is associated with FGFR3 expression. Materials and Methods: Cell proliferation and apoptosis assays were performed in minimal FGFR3 expressing U266 cells and compared to U266 cells overexpressing FGFR3 wild-type (T-U266), or Y373C (Y-U266) or K650E (K-U266) mutant FGFR3. Results: Our results suggested cell survival decreases in a dose-dependent manner. Interestingly, expression of FGFR3 protein was similarly dose dependent on bortezomib. It is confirmed the bortezomib-induced apoptotic death is correlated with FGFR3 expression. Furthermore, increased expression of p-STAT3, Mcl-1 and VEGF suggested that bortezomib resistance associated with Y373C mutation and wild-type FGFR3 may be partly mediated through p-STAT3 signaling. Conclusion: Our data indicates that Y373C mutation and wild-type FGFR3 may be associated with bortezomib-related treatment resistance in multiple myeloma.