Activation of AMP-activated protein kinase is involved in doxorubicin-induced anti-breast cancer cell proliferation / 肿瘤研究与临床

ABSTRACT

Objective To investigate the mechanism of anti-breast cancer cell proliferation induced by doxorubicin (DOX).Methods AMP-Activated Protein Kinase (AMPK) activator AICAR,AMPK siRNA,AMPK inhibitor compound C(AMPKi) and doxorubicin treated MCF-7 cells at different time points; AMPK,acetyl CoA carboxylase (ACC),p38 activation were detected by Western blot.MTT was used as cell viability assay. Results Doxorubicin-induced activation of AMPK, AMPK agonist (AICAR)or in combination with doxorubicin activated AMPK and increased MCF-7 cell proliferation rate [the difference of cell viability between group AICAR+DOX(17.7±1.6 ) ％ and group DOX(71.4±1.8 ) ％ was significant(P＜0.001)].After AMPKi or AMPK siRNA and doxorubicin combined administration, P-AMPK and P-ACC expression was significantly decreased,the level of p38 was not affected,and MCF-7 cell proliferation inhibition rate decreased [the cell viability of group AMPKi+DOX(72.7±1.8 ) ％ vs group DOX(96.3±1.7 ) ％,P＜0.001 ;group AMPK siRNA +DOX( 76.9±2.2 ) ％ vs group scramble siRNA+DOX(95.9±1.8) ％,P＜0.001].Conclusion AMPK is involved in doxorubicin-induced anti-breast cancer cell proliferation.