Insulin exacerbated high glucose-induced epithelial-mesenchymal transition in prostatic epithelial cells BPH-1 and prostate cancer cells PC-3 via MEK/ERK signaling pathway

Exp Cell Res. 2020 Sep 1;394(1):112145. doi: 10.1016/j.yexcr.2020.112145. Epub 2020 Jun 16.

Abstract

As two most common progressive diseases of aging, type 2 diabetes mellitus (T2DM) and benign prostatic hyperplasia (BPH) were all characterized by endocrine and metabolic disorders. Here, our clinical study showed that there were significant differences in fasting blood glucose (FBG), fasting insulin (FINS), insulin resistance index (HOMA-IR) and prostate volume (PV) between simple BPH patients and BPH complicated with T2DM patients. Further analysis showed that HOMA-IR was positively correlated with PV in BPH complicated with T2DM patients. The in vitro experiment results showed that high glucose (HG) promoted EMT process in a glucose-dependent manner in human prostate hyperplasia cells (BPH-1) and prostate cancer cells (PC-3), and this pathological process was exacerbated by co-culture with insulin. Mechanistically, insulin-induced exacerbation of EMT was depended on the activation of MEK/ERK signaling pathway, and we suggested that insulin and its analogs should be used very carefully for the clinical antihyperglycemic treatment of BPH complicated with T2DM patients.

Keywords: Benign prostatic hyperplasia; Epithelial-mesenchymal transition; High glucose; Insulin; MEK/ERK signaling Pathway; Type 2 diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelial-Mesenchymal Transition / drug effects
  • Epithelial-Mesenchymal Transition / physiology
  • Glucose / metabolism*
  • Glucose / pharmacology*
  • Humans
  • Insulin / pharmacology*
  • Insulin Resistance / physiology
  • Male
  • Mitogen-Activated Protein Kinase Kinases
  • Prostate / drug effects
  • Prostate / metabolism
  • Prostatic Hyperplasia / drug therapy*
  • Prostatic Hyperplasia / metabolism
  • Prostatic Hyperplasia / pathology
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Signal Transduction / drug effects

Substances

  • Insulin
  • Mitogen-Activated Protein Kinase Kinases
  • Glucose