Effects of metformin on cell proliferation and fatty acid synthase in human hepatocellular carcinoma cell line HepG2
- VernacularTitle:二甲双胍对人肝癌细胞 HepG2增殖及脂肪酸合酶的影响
- Author:
Xiaoren PENG
;
Yan LIU
;
Dajin ZOU
;
Juan LI
- Publication Type:Journal Article
- Keywords:
Metformin;
HepG2 human hepatocellular carcinoma cell line;
Fatty acid synthase;
AMP-activated protein ki-nase;
Mammalian target of rapamycin
- From:
Journal of Medical Postgraduates
2015;(4):360-364
- CountryChina
- Language:Chinese
-
Abstract:
Objective The cancer risk of patients with diabetes mellitus who are treated by metformin declines remarkably in comparison to patients receiving other drug therapies.The article was to investigate the relationship between antineopastic activity and fatty acid synthase (FASN) of metformin in human hepatocellular carcinoma cell(HCC) line HepG2. Methods HepG2 cells were treated with various concentrations of metformin( 0, 1, 5, 10, 15 mmol/L) for 24, 48 and 72 h respectively and cell growth was assessed by CCK-8 assay.Positive control(paclitaxel 10μg/mL) and negative control(metformin 0mmol/L) were set up simultaneously.After being treated with doses of metformin(0, 5, 10,15mmol/L) for 72h, protein expression levels of AMPKα、P-AMPKα、FASN、P-mTOR and P-Akt were measured by western blotting analysis and FASN mRNA expression levels were measured by RT-PCR. Results Being treated with vari-ous doses of metformin(1, 5, 10, 15 mmol/L) for 24, 48 and 72 h, the growth of HepG2 cells were inhibited by metformin in dose-dependent and time-dependent manner( P<0.05) .The growth inhibition rate approached 50%after being treated with metformin for 72 h, and the growth inhibition rate were all greater than 50%after being treated with 15 mmol/L of metformin.At 72 h after the treatment of various do-ses of metformin(0, 5, 10, 15 mmol/L) on HepG2 cells, the protein expression of P-AMPK increased with the rise of metformin concentra-tion, while the protein expressions of P-mTOR and FASN decreased as the metformin concentration increased.Compared with negative control group, the protein expression levels of P-AMPKα, P-mTOR and FASN all changed significantly in 10 mmol/L group and 15 mmol/L group(P<0.05).However, there was no significant difference as to the protein expression levels of P-Akt in various metformin concen-trations( P>0.05) .FASN mRNA expression levels decreased significantly in all metformin-treated groups( P<0.05) . Conclusion Met-formin actitiviates AMPK, inhibits mTOR and downregulates FASN, which are implicated in its antineopastic activity on HCC.Although metformin inhibits mTOR activation, it is not involved in Akt upregulation through a negative loop.
