Metformin down-regulates endometrial carcinoma cell secretion of IGF-1 and expression of IGF-1R

Asian Pac J Cancer Prev. 2015;16(1):221-5. doi: 10.7314/apjcp.2015.16.1.221.

Abstract

As metformin can inhibit endometrial carcinoma (EC) cell growth and the insulin growth factor (IGF) system is active in EC, the question of whether t can regulate endometrial carcinoma cell secretion of IGF-1 or expression of IGF-1 receptor (IGF-1R) is of interest. In this study, serum IGF-1 levels in EC patients were found to be comparable with that in the non EC patients (p>0.05). However, the IGF-1 level in the medium of cultured cells after treatment with metformin was decreased (p<0.05). IGF-1R was highly expressed in human endometrial carcinoma paraffin sections, but IGF-1R and phosphor-protein kinase B/protein kinase B (p-Akt/ Akt) expression was down-regulated after metformin treatment (p<0.05). In summary, metformin can reduce the secretion of IGF-1 by Ishikawa and JEC EC cell lines and their expression of IGF-1R to deactivate downstream signaling involving the PI-3K/Akt pathway to inhibit endometrial carcinoma cell growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma / drug therapy*
  • Carcinoma / genetics
  • Cell Line, Tumor
  • Down-Regulation / drug effects*
  • Down-Regulation / genetics
  • Endometrial Neoplasms / drug therapy*
  • Endometrial Neoplasms / genetics
  • Female
  • Humans
  • Insulin-Like Growth Factor I / genetics*
  • Metformin / pharmacology*
  • Middle Aged
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphorylation / genetics
  • Proto-Oncogene Proteins c-akt / genetics
  • Receptor, IGF Type 1 / genetics*
  • Receptor, IGF Type 1 / pharmacology*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics

Substances

  • Insulin-Like Growth Factor I
  • Metformin
  • Phosphatidylinositol 3-Kinases
  • Receptor, IGF Type 1
  • Proto-Oncogene Proteins c-akt