Metformin suppresses CRC growth by inducing apoptosis via ADORA1.
Accumulating evidence suggests that the anti-diabetic drug, metformin, exerts anti-proliferative effects in many types of cancers. However, the function and mechanisms of metformin in human colorectal cancer (CRC) remain unknown. Here, we show that metformin induces growth inhibition and apoptosis through activating AMPK-mTOR pathway in human colorectal cancer cells. Notably, metformin treatment significantly up-regulated adenosine A1 receptor (ADORA1) expression in human colorectal cancer cells, while suppression of ADORA1 activity by its specific inhibitor rescued the growth inhibition induced by metformin. Moreover, ADORA1-mediated growth inhibition and apoptosis induced by metformin is AMPK-mTOR pathway dependent in human colorectal cancer cells. Taken together, these results indicate that metformin suppresses human colorectal cancer growth by inducing apoptosis via ADORA1, which provide evidence the anti-neoplastic effects of metformin in the treatment of human colorectal cancer.
Department of gastroenterological surgery, the First Affiliated Hospital, Fujian Medical University, 20 chazhong Rd, Fuzhou 350005, Fujian Province, China, lanbin111@yahoo.com.
Bin
B
Lan
Department of Neurology, the Affiliated Union Hospital, Fujian Medical University, 29 Xinquan Rd, Fuzhou 350001, Fujian Province, China.
Jian
J
Zhang
Department of Thoracic Surgery, Shanghai, Pulmonary Hospital of Tongji University,507 Zhengmin Rd., Shanghai 200433 PR China.
Peng
P
Zhang
Department of oncological surgery, the First Hospital of Putian City, 389 longdejing, chengxiang district, Putian 351100, Fujian Province, China.
Weihong
W
Zhang
Department of gastroenterological surgery, the First Affiliated Hospital, Fujian Medical University, 20 chazhong Rd, Fuzhou 350005, Fujian Province, China.
Shugang
S
Yang
Department of Gastrointestinal medicine, the First Affiliated Hospital, Fujian Medical University, 20 chazhong Rd, Fuzhou 350005, Fujian Province, China.
Dong
D
Lu
Department of Gastrointestinal medicine, the First Affiliated Hospital, Fujian Medical University, 20 chazhong Rd, Fuzhou 350005, Fujian Province, China.
Wenqin
W
Li
Department of gastroenterological surgery, the First Affiliated Hospital, Fujian Medical University, 20 chazhong Rd, Fuzhou 350005, Fujian Province, China.
Qinbao
Q
Dai
D058907:Adenosine A1 Receptor Agonists / Q000494:pharmacology; D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045325:HCT116 Cells; D006801:Humans; D008687:Metformin / Q000494:pharmacology*; D043682:Receptor, Adenosine A1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D000970:Antineoplastic Agents; D043682:Receptor, Adenosine A1; D008687:Metformin; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases