HIF-1α silencing suppresses growth of lung adenocarcinoma A549 cells through induction of apoptosis

Mol Med Rep. 2014 Mar;9(3):911-5. doi: 10.3892/mmr.2014.1910. Epub 2014 Jan 22.

Abstract

Lung adenocarcinoma (AC) is one of the most deadly malignancies. The disease has a low five-year survival rate; therefore, the identification of novel therapeutic agents is required. This study aimed to investigate the effect of small interfering RNA (siRNA) targeting hypoxia‑inducible factor 1α (HIF‑1α) on the growth of AC A549 cells. A549 cells were transfected with various concentrations of HIF‑1α or control siRNA, and the effect on HIF‑1α expression was analyzed using quantitative polymerase chain reaction and western blot analysis. The effects of HIF-1α siRNA on growth inhibition and apoptosis were then assessed using standard methods. HIF‑1α siRNA treatment significantly reduced HIF‑1α mRNA and protein expression in A549 cells. Furthermore, the downregulation of HIF-1α expression inhibited the growth of A549 cells and induced apoptosis of A549 cells by upregulating caspase-3 expression. The present in vitro study demonstrates that the downregulation of HIF‑1α is capable of suppressing AC A549 cell growth, through the induction of apoptosis. This suggests that HIF‑1α inhibition may represent a promising strategy for the treatment of AC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Adenocarcinoma of Lung
  • Apoptosis / genetics*
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • RNA Interference*
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism
  • Up-Regulation

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit
  • RNA, Messenger
  • RNA, Small Interfering
  • Caspase 3