title: Metformin inhibits renal cell carcinoma in vitro and in vivo xenograft.
abstract: OBJECTIVE
  To evaluate the effects of metformin on renal cell carcinoma (RCC) and its underlying mechanisms.
  
  
  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.affiliation: The Third Military Medical University, Chongqing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Bo
authors.initials: B
authors.lastname: Song
authors.forename: Chunhong
authors.initials: C
authors.lastname: Jia
authors.forename: Lichao
authors.initials: L
authors.lastname: Zhang
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Bai
authors.forename: Weilie
authors.initials: W
authors.lastname: Hu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D008687:Metformin