Participation of autophagy in the cytotoxicity against breast cancer cells by cisplatin.
Participation of autophagy in the cytotoxicity against breast cancer cells by cisplatin.
复制标题
DOI：
10.3892/or.2015.4005
复制
发表时间：
2015-07
期刊：
影响因子：
4.2
通讯作者：
Meng Shen;W. Duan;Mengyao Wu;Wen-jie Wang;Lu Liu;Mengdan Xu;Jie Zhu;Dao-ming Li;Qi Gui
中科院分区：
文献类型：
--
作者：
Meng Shen;W. Duan;Mengyao Wu;Wen-jie Wang;Lu Liu;Mengdan Xu;Jie Zhu;Dao-ming Li;Qi Gui
乳腺癌是影响全世界妇女的最常见癌症之一。常规化疗仍是治疗乳腺癌的主要方法之一。自噬，也称为II型程序性细胞死亡（PCD），表现出促肿瘤发生或抗肿瘤发生功能。在本研究中，我们调查了自噬是否可能参与化疗对乳腺癌的影响。本研究应用了表阿霉素、多西他赛、甲氨蝶呤、环磷酰胺、氟尿嘧啶（5-FU）和顺铂。所有这些化疗药物对乳腺癌细胞都具有细胞毒性。DsRed-LC 3报告基因分析显示，只有多西他赛和顺铂诱导自噬。自噬抑制剂3-甲基腺嘌呤（3-MA）增强了多西他赛的细胞毒性，但削弱了顺铂的细胞毒性，表明多西他赛刺激促肿瘤发生的自噬，而顺铂诱导的自噬可能是抗肿瘤的。Real-time PCR结果显示，顺铂上调了AMBRA 1、ATG 3、ATG 4C、ATG 4D、ATG 5、ATG 7、ATG 13、ATG 14、ATG 16 L2、Beclin 1、DRAM 1、GABARAP、GABARAPL 1、GABARAPL 2、HDAC 6、IRGM、MAP 1 LC 3B和ULK 1等多个自噬相关基因，表明顺铂通过多种机制诱导自噬。
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.