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- Title
Role of metformin in inhibiting estrogen-induced proliferation and regulating ERα and ERβ expression in human endometrial cancer cells.
- Authors
JINGBO ZHANG; HUI XU; XUEYAN ZHOU; YANYU LI; TONG LIU; XIAOXING YIN; BEI ZHANG
- Abstract
Diabetes mellitus (DM) is an important factor that contributes to the development of type I endometrial cancer (EC). Previous studies have demonstrated that metformin decreases mortality and risk of neoplasms in patients with DM. Since estrogen and estrogen receptor (ER) expression has been associated with the development of EC, the present study aimed to investigate the effects of metformin on cell proliferation and ER expression in EC cell lines that are sensitive to estrogen. The viability and proliferation of Ishikawa and HEC-1-A cells were measured following treatment with metformin and/or a 5' AMP-activated protein kinase (AMPK) inhibitor (compound C) with or without treatment with estradiol (E2). In addition, the levels of ERa, ERß, AMPK, ribosomal protein S6 kinase β-1 (p70S6K), myc proto-oncogene protein (c-myc) and proto-oncogene c-fos (c-fos) were measured following treatment. Metformin significantly decreased E2-stimulated cell proliferation; an effect that was rescued in the presence of compound C. Metformin treatment markedly increased the phosphorylation of AMPK while decreasing p70S6K phosphorylation, indicating that metformin exerts its effects through stimulation of AMPK and subsequent inhibition of the mammalian target of rapamycin (mTOR) signaling pathway. In addition, metformin significantly inhibited ERa expression while increasing ER&3946; expression, whereas treatment with compound C reversed these effects. Reverse transcription-quantitative polymerase chain reaction analysis demonstrated that c-fos and c-myc expression were attenuated by metformin, an effect that was rescued in the presence of compound C. Therefore, metformin regulates the expression of ERs, and inhibits estrogen-mediated proliferation of human EC cells through the activation of AMPK and subsequent inhibition of the mTOR signaling pathway.
- Subjects
TREATMENT of endometrial cancer; METFORMIN; ESTROGEN receptors; PROTEIN kinases; RIBOSOMAL proteins
- Publication
Oncology Letters, 2017, Vol 14, Issue 4, p4949
- ISSN
1792-1074
- Publication type
Article
- DOI
10.3892/ol.2017.6877