Afatinib Sensibilizes Multidrug-resistant Human Ovarian Cancer Cells to Adriamycin and Related Mechanisms

Objective To investigate the effect of afatinib on the chemosensitization of multidrug-resistant A2780T cells to adriamycin and related mechanism.

Methods MTT assay was used to investigate the effect of afatinib on the IC₅₀ values of adriamycin in A2780 and A2780T cells. The efflux function and ATPase activity of ABCB1 were investigated by rhodamine 123 accumulation assay and ABCB1-Glo^TM Assay Systems, respectively. The expression of EGFR, HER-2, p-EGFR, p-HER-2 and ABCB1 were investigated by Western blot. RT-PCR assay was applied to test the mRNA expression of MDR1 in A2780T cells.

Results Afatinib at nontoxic concentrations significantly decreased the IC₅₀ of adriamycin in A2780T cells (P < 0.05), while no effect in A2780 cells. Afatinib could inhibit the efflux function and increase the ATPase activity of ABCB1 in a concentration-dependent manner(P < 0.05). Afatinib inhibited the phosphorylation of EGFR and HER-2, and decreased the expression of ABCB1 protein and MDR1 mRNA in A2780T cells.

Conclusion Afatinib could sensibilize multidrug-resistant A2780T cells to adriamycin by inhibiting the efflux function and downregulating ABCB1 expression.