Resumen de CIP2A silencing alleviates doxorubicin resistance in MCF7/ADR cells through activating PP2A and autophagy
Background Cancerous inhibitor of protein phosphatase 2A (CIP2A) plays a critical role in the pathogenesis of various types of cancer. Here, we investigated whether manipulating CIP2A abundance could enhance the treatment efects of doxorubicin in MCF-7/ADR cells.
Methods CIP2A silencing was achieved by specifc siRNAs. Proliferation of breast cancer cell line MCF-7/ADR under efective doxorubicin concentrations after CIP2A silencing was examined by MTT assay. Wound healing assay was performed to quantify cell migration and caspase-3/-7 activities were measured for assessing the extent of apoptosis.
Results First, our data confrmed that MCF-7/ADR cell proliferation was suppressed by doxorubicin in a dose-dependent manner. Additionally, knocking down of CIP2A could further decrease MCF-7 cell proliferation and migration, even in the presence of doxorubicin. Mechanistically, we have found that CIP2A silencing promoted cell apoptosis relative to doxorubicin alone or vehicle control groups. Lastly, phosphatase2A (PP2A) activity was potentiated and the autophagy markers, LC3B and Beclin1, were upregulated after knocking down CIP2A.
Conclusion Our fndings support the potential benefts of using CIP2A inhibitor as a therapeutic agent to treat doxorubicinresistant breast cancer.
