Retinoic acid aliphatic amide inhibits the AMPK-HIF-1α pathway in human ovarian cancer

Int J Clin Exp Pathol. 2015 Jun 1;8(6):6416-24. eCollection 2015.

Abstract

Ovarian carcinoma the commonly observed gynecological cancers has a high mortality rate. In the present study effect of retinoic acid aliphatic amide (RACA) in ovarian cancer cells was investigated using proliferation, migration and invasion assays. Western blot was used to examine the Bcl-2, cleaved caspase 3, p-ERK, MMP-2, p-FAK, P-P38, p-AMPKα and HIF-1α protein expression. CoCl2 was used to induce HIF-1α expression in SKOV3ip. 1 and HEY-A8 cells. The results revealed that RACA treatment prompted cell proliferation, invasion and migration but inhibited apoptosis of SKOV3ip. 1 and HEY-A8 cells. RACA treatment also induced upregulation of Bcl-2 and MMP-2, activation of p-P38, p-ERK and p-FAK, inhibition of cleaved caspase 3. RACA treatment also caused upregulatation of HIF-1α in ovarian cells with the activation of p-AMPKα. Upregulation of HIF-1α expression in CoCl2-treated cancer cells resulted in decrease in SDHB. Thus RACA plays a key role in cell proliferation, invasion, migration and apoptosis of human ovarian carcinoma through AMPK-HIF-1α pathway.

Keywords: AMPK; HIF-1α; Tumor progression; apoptosis; gene silence; ovarian carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Female
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Neoplasm Invasiveness / pathology
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Tretinoin / analogs & derivatives*
  • Tretinoin / pharmacology*

Substances

  • Antineoplastic Agents
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Tretinoin
  • AMP-Activated Protein Kinases