Adriamycin Induced Chemoresistance of Human TNBC MDA-MB-468 Cells Through Stat3-cMyc Signal Pathway

Abstract

Objective To investigate the chemoresistance of human triple-negative breast cancer(TNBC) MDA-MB-468 cells induced by adriamycin(ADM) and the underlying mechanism. Methods MDA-MB-468 cells were treated with ADM at different concentrations for 24h, then MTT assay was used to detect the inhibitory rate of cell growth and the sensitivity of MDA-MB-468 cells to ADM. Immunofluorescence staining was used to detect the expression level of ABCG2 and Western blot was used to test the expression levels of phosphorylated Stat3(p-Stat3), cMyc and ABCG2. Results The sensitivity of MDA-MB-468/ADM to ADM was remarkably reduced and the expression of drug resistance protein ABCG2 was increased obviously in MDA-MB-468/ADM cells. In addition, the expressions of p-Stat3, cMyc and ABCG2 were much higher in MDA-MB-468/ADM cells than those in MDA-MB-468 cells. Interestingly, when the phosphorylation of Stat3 was inhibited by WP1066, the expressions of cMyc and ABCG2 were downregulated; furthermore, the sensitivity of MDA-MB-468/ADM cells to ADM was increased (P < 0.05). Conclusion ADM could induce the chemoresistance of human TNBC MDA-MB-468 cells through Stat3-cMyc signal pathway.

Keywords

• triple-negative breast cancer(tnbc)
• adriamycin(adm)
• chemoresistance
• stat3
• cmyc
• abcg2