Upregulation of microRNA-451 increases cisplatin sensitivity of non-small cell lung cancer cell line (A549)

J Exp Clin Cancer Res. 2011 Feb 17;30(1):20. doi: 10.1186/1756-9966-30-20.

Abstract

Background: Recently, miR-451 as a tumor suppressor has been reported in other studies. However, whether miR-451 can affect the sensitivity of non-small cell lung cancer (NSCLC) cells to cisplatin (DDP) remains unclear. The aim of this study is to evaluate the roles of miR-451 in the sensitivity of NSCLC cells to DDP.

Methods: Quantitative RT-PCR assay was performed to detect the expression of miR-451 in 10 pairs of NSCLC and noncancerous tissue samples. pcDNA-GW/EmGFP-miR-451 was stably transfected into NSCLC cell line (A549). Then, the effects of miR-451 upregulation on growth, colony formation and apoptosis of A549 cells were investigated. Finally, the effects of miR-451 upregulation on in vitro and in vivo sensitivity of A549 cells of DDP were also determined.

Results: The level of miR-451 expression in NSCLC tissues was significantly higher than that in corresponding noncancerous tissues. Ectopic overexpression of miR-451 could significantly inhibit growth and induce apoptosis of A549 cells. Moreover, ectopic overexpression of miR-451 could sensitize A549 cells to DDP possibly by increasing DDP-induced apoptosis which might be associated with the inactivation of Akt signaling pathway.

Conclusions: This study demonstrated for the first time that combination of DDP application with miR-451 upregulation might be a potential strategy for the treatment of human NSCLC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / genetics
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Cell Line, Tumor
  • Cisplatin / therapeutic use*
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Formazans
  • Gene Expression Regulation, Neoplastic
  • Genetic Vectors
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / genetics*
  • Signal Transduction / genetics
  • Tetrazolium Salts
  • Transfection
  • Up-Regulation / genetics

Substances

  • Antineoplastic Agents
  • Formazans
  • MIRN451 microRNA, human
  • MicroRNAs
  • Tetrazolium Salts
  • MTT formazan
  • Cisplatin