GSTP1 promote breast cancer cell proliferation and adriamycin resistance by regulating STAT3 signal pathway
Objective To investigate the effect and mechanism of glutathione S-transferase P1(GSTP1)on proliferation and adriamycin resistance of breast cancer MCF-7 cells.Methods The expression levels of GSTP1 in MCF-7 and MCF-7/ADR cell lines were assessed via Western blotting.Overexpression of GSTP1 was achieved by transfection of Flag-GSTP1 plasmid in MCF-7 cells,and interference with GSTP1 expression was achieved by transfection of GSTP1 knockdown lentivirus(shGSTP1)in MCF-7/ADR cells.Proliferation,doxorubicin resistance and apoptosis levels of the cell lines after transfection were evaluated via colony formation assay,CCK-8 method and flow cytometry.Finally,the impact of GSTP1 expression level on the activation of the STAT3 pathway was investigated through Western blotting.Results GSTP1 exhibited markedly low expression in MCF-7 cells,significantly lower than that in the MCF-7/ADR cell line.The number of clone formation in MCF-7/ADR cells overexpressing GSTP1 was significantly higher than that in wild-type MCF-7 cells(P<0.05).Overexpression of GSTP1 significantly enhanced the proliferative capacity of MCF-7 cells,whereas interference with GSTP1 expression levels in the MCF-7/ADR cell line significantly inhibited cell proliferation(P<0.05).CCK-8 result demonstrated a positive correlation between GSTP1 expression levels and doxorubicin resistance in MCF-7 cells treated with doxorubicin concentrations of 0.1,1,10,and 50 μmol/ml(P<0.05).Flow cytometry analysis revealed that the apoptosis rates of the GSTP1 overexpression group(Flag-GSTP1)and the control group(Flag)were(11.41±1.16)%and(21.1±1.72)%,respectively.GSTP1 overexpression significantly inhibited doxorubicin-induced cell apoptosis(P<0.05).Western blotting further confirmed that high expression of GSTP1 activated the STAT3 signaling pathway,while inhibiting STAT3 in the MCF-7/ADR cell line significantly reduced the expression levels of GSTP1(P<0.05).Conclusion GSTP1 regulates the proliferation of MCF-7 cells and drug resistance to adriamycin by up-regulating STAT3 expression.
Breast cancerGlutathione S-transferase P1ProliferationAdriamycin resistance
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