Gene interactions and pathways from curated databases and text-mining
Urol Oncol 2013, PMID: 21676631

Metformin inhibits renal cell carcinoma in vitro and in vivo xenograft.

Liu, Jun; Li, Ming; Song, Bo; Jia, Chunhong; Zhang, Lichao; Bai, Xiaochun; Hu, Weilie

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.

Diseases/Pathways annotated by Medline MESH: Carcinoma, Renal Cell, Kidney Neoplasms
Document information provided by NCBI PubMed

Text Mining Data

mammalian target of rapamycin (mTOR) ⊣ AMP activated protein kinase (AMPK): " 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 "

Manually curated Databases

No curated data.