Metformin inhibits lung cancer cells proliferation mediated by activation of p53 via ribosome pretein S7-MDM2 interaction

• Main Authors: Chun-Ching Kuo, 郭淳靖
• Other Authors: I-Tsuen Chen
• Format: Others
• Language: zh-TW
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/18299477905937555751

碩士 === 國立陽明大學 === 醫學生物技術暨檢驗學系暨研究所 === 99 === Metformin is an antidiabetic drug for type 2 diabetes. Epidemic studies have revealed that metformin could reduce the risk of cancer in diabetic patients. Recently, many studies have shown that metformin exerted an antitumoral effect both in vitro and in vivo. We investigated the effects of metformin on the proliferation in A549 lung cancer cells. Our data show that metformin inhibited cell growth and exhibited G1 cell cycle arrest. Both effects were found to be p53-dependent. Furthermore, we revealed that metformin treatment resulted in inhibition of pre-rRNA synthesis and redistribution of the ribosomal protein S7 in the nucleus. The latter led to enhancement of the interaction between MDM2 and ribosomal protein S7 and a decreased interaction between MDM2 & p53. Finally, the rpS7 gene knockdown reduced p53 activation by metformin. Furthermore, ecotopic rpS7 expression enhanced p53 activation by metformin. These results suggest that metformin may trigger the ribosome stress that induces p53 activation and inhibits lung cancer cell growth via rpS7-MDM2-p53 pathway.