Reversal Effect of Apatinib on P-gp-mediated Multidrug Resistance of Human Breast Cancer and Its Mechanisms

Objective To investigate the reversal effect of apatinib on the multidrug resistance of human breast cancer and the underlying mechanisms.

Methods MCF-7 and MCF-7/ADR cells were treated with different concentrations of apatinib for 48h. Cell proliferation was measured by MTT assay. The reversal effect of apatinib on the multidrug resistance of MCF-7/ADR cells to paclitaxel and adriamycin were investigated by MTT assay. The effects of apatinib on the accumulation of rhodamine 123 in MCF-7 and MCF-7/ADR cells were investigated by flow cytometry. The effect of apatinib on ATPase activity of P-gp was investigated by Pgp-Glo^TM Assay Systems. The effects of apatinib on the expression of P-gp, AKT and p-AKT were investigated by Western blot.

Results Apatinib could reverse the multidrug resistance of MCF-7/ADR cells to paclitaxel and adriamycin, increase the accumulation of rhodamine 123 in MCF-7/ADR cells and the ATPase activity of P-gp in a concentration-dependent manner (P < 0.05). Apatinib had no effect on the expression of P-gp or the phosphorylation of AKT.

Conclusion Apatinib could reverse the P-gp-mediated multidrug resistance of human breast cancer cell line MCF-7/ADR by inhibiting the efflux function of P-gp.