[Frontiers in Bioscience, Landmark, 22, 248-257, January 1, 2017]

Metformin suppresses CRC growth by inducing apoptosis via ADORA1

Bin Lan 1 , Jian Zhang 2 , Peng Zhang 3 , Weihong Zhang 3 , Shugang Yang 1 , Dong Lu 4 , Wenqin Li 4 , Qinbao Dai 1

1Department of Gastroenterological Surgery, The First Affiliated Hospital, Fujian Medical University, 20 Chazhong Rd, Fuzhou 350005, Fujian Province, China, 2Department of Neurology, The Affiliated Union Hospital, Fujian Medical University, 29 Xinquan Rd, Fuzhou 350001, Fujian Province, China, 3Department of Oncological Surgery, The First Hospital of Putian City, 389 Longdejing, Chengxiang District, Putian 351100, Fujian Province, China, 4Department of Gastrointestinal Medicine, The First Affiliated Hospital, Fujian Medical University, 20 Chazhong Rd, Fuzhou 350005, Fujian Province, China, 5Department of Thoracic Surgery, Shanghai, Pulmonary Hospital of Tongji University, 507 Zhengmin Rd., Shanghai 200433 PR China


1. Abstract
2. Introduction
3. Material and methods
    3.1. Cell lines and culture
    3.2. Cell proliferation assay
    3.3. Soft agar colony formation assay
    3.4. Cell apoptosis analysis
    3.5. Gene expression profiles chip analysis
    3.6. Quantitative RT-PCR analysis
    3.7. Western blot analysis
    3.8. Statistical analysis
4. Results
    4.1. Metformin suppresses the proliferation of human colorectal cancer cells
    4.2. Metformin induces apoptosis in human colorectal cancer cells
    4.3. Metformin treatment up-regulates ADORA1 expression in human colorectal cancer cells
    4.4. Inhibition of ADORA1 rescues the growth inhibition induced by metformin in human colorectal cancer cells
    4.5. ADORA1 mediates the growth inhibition and apoptosis induced by metformin in an AMPK-mTOR pathway dependent manner
5. Discussion
6. Acknowledgements
7. References


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.


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Key Words: Metformin, Colorectal Cancer, Adenosine A1 Receptor, Cell Growth, Apoptosis

Send correspondence to: Bin Lan, Department of Gastroenterological Surgery, the First Affiliated Hospital, Fujian Medical University, 20 Chazhong Rd, Fuzhou 350005, Fujian Province, China, Tel: 8613705006909, Fax: 86059187981028, E-mail: lanbin111@yahoo.com.