Participation of autophagy in the cytotoxicity against breast cancer cells by cisplatin.

Abstract

Breast cancer is one of the most common cancers affecting women worldwide. Conventional chemotherapy is still one of the major approaches to the treatment of breast cancer. Autophagy, also termed as type II programmed cell death (PCD), exhibits either a protumorigenic or antitumorigenic function. In the present study, we investigated whether autophagy could be involved in the effect of chemotherapy against breast cancer. Epirubicin, docetaxel, methotrexate, cyclophosphamide, fluorouracil (5-FU) and cisplatin were applied in the present investigation. All of these chemotherapeutics presented cytotoxicity against breast cancer cells. DsRed-LC3 reporter assay revealed that only docetaxel and cisplatin induced autophagy. Autophagy inhibitor 3-methyladenine (3-MA) strengthened the cytotoxicity of docetaxel, yet impaired the cytotoxicity of cisplatin, suggesting that docetaxel stimulates protumorigenic autophagy, while cisplatin-induced autophagy could be antitumorigenic. Real-time PCR revealed that cisplatin upregulated multiple autophagy-related genes, including AMBRA1, ATG3, ATG4C, ATG4D, ATG5, ATG7, ATG13, ATG14, ATG16L2, Beclin1, DRAM1, GABARAP, GABARAPL1, GABARAPL2, HDAC6, IRGM, MAP1LC3B and ULK1, indicating that cisplatin induced autophagy through a multiple mechanism involved manner.