OBJECTIVE: To evaluate the effects of metformin on renal cell carcinoma (RCC) and its underlying mechanisms. MATERIALS AND METHODS: We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and colony formation assays to investigate the effects of metformin on RCC cell growth. Flow cytometry was used to evaluate the cell cycle changes after metformin treatment. We further determined the possible signaling molecules involved in this process by immunoblot analysis of various proteins. Furthermore, a xenograft model was used to study the effects of metformin on RCC tumor growth. RESULTS: We demonstrated that metformin effectively inhibits cell proliferation in 786-O and OS-RC-2 RCC cell lines. Moreover, metformin down-regulated cyclin D1 expression and induced G0/G1 cell cycle arrest in these cells. Further study revealed metformin induced the activation of AMP-activated protein kinase (AMPK), and inhibited mammalian target of rapamycin (mTOR), which is a central regulator of protein synthesis and cell growth, and negatively regulated by AMPK. Most importantly, daily treatment of mice with metformin prevented RCC tumor growth in a xenograft model. CONCLUSIONS: Metformin was able to induce G0/G1 cell cycle arrest and inhibit RCC growth in vitro and in vivo. These results suggest that metformin may be a potential therapeutic agent for the treatment of RCC.
OBJECTIVE: To evaluate the effects of metformin on renal cell carcinoma (RCC) and its underlying mechanisms. MATERIALS AND METHODS: We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and colony formation assays to investigate the effects of metformin on RCC cell growth. Flow cytometry was used to evaluate the cell cycle changes after metformin treatment. We further determined the possible signaling molecules involved in this process by immunoblot analysis of various proteins. Furthermore, a xenograft model was used to study the effects of metformin on RCC tumor growth. RESULTS: We demonstrated that metformin effectively inhibits cell proliferation in 786-O and OS-RC-2 RCC cell lines. Moreover, metformin down-regulated cyclin D1 expression and induced G0/G1 cell cycle arrest in these cells. Further study revealed metformin induced the activation of AMP-activated protein kinase (AMPK), and inhibited mammalian target of rapamycin (mTOR), which is a central regulator of protein synthesis and cell growth, and negatively regulated by AMPK. Most importantly, daily treatment of mice with metformin prevented RCC tumor growth in a xenograft model. CONCLUSIONS:Metformin was able to induce G0/G1 cell cycle arrest and inhibit RCC growth in vitro and in vivo. These results suggest that metformin may be a potential therapeutic agent for the treatment of RCC.
Authors: Roger C Zhu; Kirk Rattanakorn; Steven Pham; Divya Mallam; Thomas McIntyre; Moro O Salifu; Irini Youssef; Samy I McFarlane; Shivakumar Vignesh Journal: Colorectal Cancer Date: 2017-06-21
Authors: Amira Elgogary; Qingguo Xu; Brad Poore; Jesse Alt; Sarah C Zimmermann; Liang Zhao; Jie Fu; Baiwei Chen; Shiyu Xia; Yanfei Liu; Marc Neisser; Christopher Nguyen; Ramon Lee; Joshua K Park; Juvenal Reyes; Thomas Hartung; Camilo Rojas; Rana Rais; Takashi Tsukamoto; Gregg L Semenza; Justin Hanes; Barbara S Slusher; Anne Le Journal: Proc Natl Acad Sci U S A Date: 2016-08-24 Impact factor: 11.205
Authors: A Ari Hakimi; Ling Chen; Philip H Kim; Daniel Sjoberg; Leonard Glickman; Marc R Walker; Paul Russo Journal: Can Urol Assoc J Date: 2013 Nov-Dec Impact factor: 1.862