Anti-proliferative effect of salinomycin on doxorubicin-resistant human breast cancer MCF-7/DOX cells
10.3969/j.issn.1001-1978.2015.04.022
- VernacularTitle:Salinomycin对乳腺癌阿霉素耐药细胞株MCF-7／DOX的增殖抑制作用及机制
- Author:
Hao LIU
;
Minying LU
;
Zhimin HE
- Publication Type:Journal Article
- Keywords:
breast cancer;
salinomycin;
doxorubicin resistance;
cell apoptosis;
ROS;
mitochondrial mem-brane potential
- From:
Chinese Pharmacological Bulletin
2015;(4):549-554
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the anti-proliferative effect of salinomycin on doxorubicin-resistant human breast cancer MCF-7 /DOX cells.Methods MCF-7 and MCF-7 /DOX cells were treated or untreated with salinomycin.Cell viability was detected by MTS assay. Cell apoptosis was detected by Annexin V-FITC /PI as-say.Reactive oxygen species (ROS)was measured by DCFH-DA staining.Mitochondrial membrane potential was measured by JC-1 assay.The expression of apopto-sis related proteins BAX, BCL-2, caspase-3, and caspase-9 were evaluated by Western blot analysis. Results The cell viability was significantly reduced by salinomycin treatment in a dose-dependent manner. The flow cytometry results showed that salinomycin in-duced MCF-7 /DOX cell apoptosis,increased ROS pro-duction,and decreased mitochondrial membrane poten-tial.Furthermore,salinomycin decreased the expres-sion of BCL-2,and increased the expression of BAX, cleaved caspase-3,and cleaved caspase-9.Moreover, the antioxidant N-acetylcysteine (NAC ) markedly blocked the above effects.Conclusions Our results suggest that salinomycin-induced apoptosis in MCF-7 /DOX is associated with induction of ROS production, and activation of mitochondria apoptosis pathway, which may become a potential chemotherapeutic agent for the therapy of doxorubicin resistant breast cancer.
