Open Access

Regulation of insulin‑like growth factor signaling by metformin in endometrial cancer cells

  • Authors:
    • Ya Xie
    • Jing‑Lu Wang
    • Mei Ji
    • Zhong‑Fu Yuan
    • Zheng  Peng
    • Yi  Zhang
    • Jian‑Guo Wen
    • Hui‑Rong Shi
  • View Affiliations

  • Published online on: August 20, 2014     https://doi.org/10.3892/ol.2014.2466
  • Pages: 1993-1999
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Obesity, diabetes and insulin resistance are marked risk factors that promote the development of type I endometrial cancer. Previous studies have demonstrated that insulin‑like growth factor 1 (IGF‑1) and IGF‑2 promote cell proliferation in endometrial cancer cells, while metformin reverses this effect and inhibits cell proliferation. However, the effects of metformin on the regulation of the IGF signaling pathway are unclear. The aim of this study was to investigate the regulation of IGF signaling by metformin in endometrial cancer cells, and to determine the effects of metformin combined with IGF‑1 receptor (IGF‑1R) inhibitor on cell proliferation and apoptosis. Cell proliferation was assessed following exposure of Ishikawa and HEC‑1B endometrial cancer cell lines to metformin and/or the IGF‑1R inhibitor, PPP. Apoptosis was assessed by TdT‑mediated dUTP nick end labeling assay. Metformin was observed to downregulate IGF‑1R and upregulate IGF binding protein‑1 (IGFBP‑1) mRNA and protein expression, while compound C, an adenosine monophosphate protein kinase inhibitor, reversed this effect. Metformin administered with PPP inhibited endometrial cancer cell proliferation to a greater degree than treatment with either agent alone. At high concentrations (1 or 2 mM), metformin induced apoptosis in endometrial cancer cells. Metformin combined with IGF‑1R axis inhibitors may act synergistically to kill tumor cells, as metformin was shown to delay and prevent IGF‑1R feedback. In conclusion, this study supported the results of animal studies and subclinical studies, demonstrating the feasibility of metformin combined with IGF‑1R axis inhibitors in the treatment of endometrial cancer.
View Figures
View References

Related Articles

Journal Cover

November-2014
Volume 8 Issue 5

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Xie Y, Wang JL, Ji M, Yuan ZF, Peng Z, Zhang Y, Wen JG and Shi HR: Regulation of insulin‑like growth factor signaling by metformin in endometrial cancer cells. Oncol Lett 8: 1993-1999, 2014.
APA
Xie, Y., Wang, J., Ji, M., Yuan, Z., Peng, Z., Zhang, Y. ... Shi, H. (2014). Regulation of insulin‑like growth factor signaling by metformin in endometrial cancer cells. Oncology Letters, 8, 1993-1999. https://doi.org/10.3892/ol.2014.2466
MLA
Xie, Y., Wang, J., Ji, M., Yuan, Z., Peng, Z., Zhang, Y., Wen, J., Shi, H."Regulation of insulin‑like growth factor signaling by metformin in endometrial cancer cells". Oncology Letters 8.5 (2014): 1993-1999.
Chicago
Xie, Y., Wang, J., Ji, M., Yuan, Z., Peng, Z., Zhang, Y., Wen, J., Shi, H."Regulation of insulin‑like growth factor signaling by metformin in endometrial cancer cells". Oncology Letters 8, no. 5 (2014): 1993-1999. https://doi.org/10.3892/ol.2014.2466