The Reversing and Molecular Mechanisms of miR-34c on the MCF-7/DOX Cells with Doxorubicin-Resistance

Abstract: miR-34 played an important role in tumor development and progress， but there were few studies on the function of miR-34 in drug resistance. To elucidate the function and mechanism of exogenous miR-34c involved in drug resistance in the breast cancer cells， miR-34c mimics were used to transfect into MCF-7/DOX cells with doxorubicin-resistance. The expression of miR-34c was analyzed by Real-time RT-PCR. Cell viability was analyzed by MTS assay. Cell cycle distribution and apoptosis were detected by PI and Annexin V/PI staining， respectively. The expressions of the drug-resistant related protein MDR and MRP， and cell proliferation and apoptosis related protein Bcl-2 and E2F3 were analyzed by Real-time RT-PCR and Western blot. Our results showed that miR-34c was significantly down-regulated in MCF-7/DOX cells， and overexpression of miR-34c increased sensitivity to doxorubicin in MCF-7/DOX cells. Flow cytometry analysis showed that miR-34c could induce G2 cell cycle arrest and cell apoptosis. Furthermore， miR-34c did not affect the expression of MDR and MRP， but sig中 nificantly inhibited the mRNA and protein expression of Bcl-2 and E2F3. Our results suggested that miR-34c could directly target and inhibit Bcl-2 and E2F3 expression， and induced G2 cell cycle arrest and apoptosis， which in turn increased sensitivity to doxorubicin in MCF-7/DOX cells.

CSTR: 32200.14.cjcb.2015.02.0010