مقاله Metformin reverses multidrug resistance and epithelial–mesenchymal transition (EMT) via activating AMP-activated protein kinase (AMPK) in human breast cancer cells : تی پی بین

خلاصه مقاله

Breast cancer is the most frequently diagnosed tumor type and the primary leading cause of cancer deaths in women worldwide and multidrug resistance is the major obstacle for breast cancer treatment improvement. Emerging evidence suggests that metformin, the most widely used antidiabetic drug, resensitizes and cooperates with some anticancer drugs to exert anticancer effect. However, there are no data regarding the reversal effect of metformin on chemoresistance in breast cancer. In the present study, we investigated the resistance reversal effect of metformin on acquired multidrug-resistant breast cancer cells MCF-7/5-Fu derived from MCF-7 breast cancer cells and innate multidrug-resistant MDA-MB-231 breast cancer cells, and we found that metformin resensitized MCF7/5-FU and MDA-MB-231 to 5-fluorouracil (5-FU), adriamycin, and paclitaxel. We also observed that metformin reversed epithelial–mesenchymal transition (EMT) phenotype and decreased the invasive capacity of MCF7/5-FU and MDA-MB-231 cells. However, there were no significant changes upon metformin-treated MCF7 cells. Moreover, we found metformin treatment activated AMPK signal pathway in MCF7/5-FU and MDA-MB-231 cells and compound C, the AMPK inhibitor, could partly abolish the resensitization and EMT reversal effect of metformin. To the best of our knowledge, we are the first to report that metformin can resensitize multidrug-resistant breast cancer cells due to activating AMPK signal pathway. Our study will help elucidate the mechanism of chemoresistance and establish new strategies of chemotherapy for human breast cancer.

نویسندگان

Chen Qu [ Cancer Research Institute and Cancer Hospital, Guangzhou Medical University, Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, People’s Republic of China ]

Weijia Zhang [ Cancer Research Institute and Cancer Hospital, Guangzhou Medical University, Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, People’s Republic of China ]

Guopei Zheng [ Cancer Research Institute and Cancer Hospital, Guangzhou Medical University, Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, People’s Republic of China ]

Zijuan Zhang [ Cancer Research Institute and Cancer Hospital, Guangzhou Medical University, Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, People’s Republic of China ]

Jiang Yin [ Cancer Research Institute and Cancer Hospital, Guangzhou Medical University, Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, People’s Republic of China ]

کلمات کلیدی

Breast cancer Multidrug resistance Metformin EMT

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Molecular and Cellular Biochemistry 2013

Molecular and Cellular Biochemistry: An International Journal for Chemical Biology in Health and Disease publishes original research papers and short communications in all areas of the biochemical sciences, emphasizing novel findings relevant to the biochemical basis of cellular function and disease processes, as well as the mechanics of action of hormones and chemical agents. Coverage includes membrane transport, receptor mechanism, immune response, secretory processes, and cytoskeletal function, as well as biochemical structure-function relationships in the cell. In addition to the reports of original research, the journal publishes state of the art reviews. Specific subjects covered by Molecular and Cellular Biochemistry include cellular metabolism, cellular pathophysiology, enzymology, ion transport, lipid biochemistry, membrane biochemistry, molecular biology, nuclear structure and function, and protein chemistry.

حوزه های تحت پوشش : Biochemistry, general, Medical Biochemistry, Oncology, Cardiology