FGF2 confers chemo-resistance of breast cancer cells by activating Akt-mTOR signal / 实用医学杂志

ABSTRACT

] Objective To explore the role and mechanisms of FGF2 in chemo?resistance in breast cancer. Methods The inhibitors for different signal pathway were used to treat two drug?resistant breast cancer cell lines MCF?7/5?Fu and T47D/5?Fu established in our lab. MTS assay was used to determine chemo?sensitivity and Hoechst stain was used to measure apoptosis. Protein activation and FGF2 protein level in cell culture medium were detected by western blot and ELISA respectively. Results Akt inhibitor MK?2206 (20 nM) and mTOR inhibitor AZD8055 (2 nM) significantly reversed the chemo?resistance of MCF?7/5?Fu and T47D/5?Fu cell lines to 5?Fu and paclitaxel, but ERK1/2 inhibitor SCH772984 showed no significant effect. Compared to parent cell lines MCF?7 and T47D, p?Akt and p?S6K (represented as mTORactivity) levels were obviously up?regulated in MCF?7/5?Fu and T47D/5?Fu cell lines, and so do the FGF2 mRNA level and FGF2 protein level from culture medium. Moreover, FGFR inhibitor AZD4547 (4 nM) markedly reversed the chemo?resistance of MCF?7/5?Fu and T47D/5?Fu cell lines to 5?Fu and paclitaxel and down?regulated activation of FGFR?Akt?mTOR signal pathway. In agreement, FGF2 protein (10ng/ml) enhanced the chemo?resistance of MCF?7 and T47D cell lines to 5?Fu and paclitaxel and up?regulated activation of FGFR?Akt?mTOR signal pathway. Conclusion Activation of FGF2?FGFR?Akt?mTOR signal pathway promoted chemo?resistance of breast cancer cells.