Use of Metformin Alone Is Not Associated with Survival Outcomes of Colorectal Cancer Cell but AMPK Activator AICAR Sensitizes Anticancer Effect of 5-Fluorouracil through AMPK Activation |
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| Authors: | Xinbing Sui Yinghua Xu Jie Yang Yong Fang Haizhou Lou Weidong Han Maolin Zhang Wei Chen Kaifeng Wang Da Li Wei Jin Fang Lou Yu Zheng Hong Hu Liu Gong Xiaoyun Zhou Qin Pan Hongming Pan Xian Wang Chao He |
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| Affiliation: | 1. Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China.; 2. Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China.; 3. Department of Colorectal Surgery, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China.; Massachusetts Eye & Ear Infirmary, Harvard Medical School, United States of America, |
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| Abstract: | Colorectal cancer (CRC) is still the third most common cancer and the second most common causes of cancer-related death around the world. Metformin, a biguanide, which is widely used for treating diabetes mellitus, has recently been shown to have a suppressive effect on CRC risk and mortality, but not all laboratory studies suggest that metformin has antineoplastic activity. Here, we investigated the effect of metformin and AMPK activator AICAR on CRC cells proliferation. As a result, metformin did not inhibit cell proliferation or induce apoptosis for CRC cell lines in vitro and in vivo. Different from metformin, AICAR emerged antitumor activity and sensitized anticancer effect of 5-FU on CRC cells in vitro and in vivo. In further analysis, we show that AMPK activation may be a key molecular mechanism for the additive effect of AICAR. Taken together, our results suggest that metformin has not antineoplastic activity for CRC cells as a single agent but AMPK activator AICAR can induce apoptosis and enhance the cytotoxic effect of 5-FU through AMPK activation. |
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