Up-regulation of Fas reverses cisplatin resistance of human small cell lung cancer cells

J Exp Clin Cancer Res. 2010 May 14;29(1):49. doi: 10.1186/1756-9966-29-49.

Abstract

Background/aim: Fas/FasL system is a major regulator of apoptosis. The mechanisms by which Fas mediates cisplatin resistance remain unclear. The aim of this study is to explore the effect of Fas over-expression on cisplatin resistance of small cell lung cancer cells and its possible mechanisms.

Materials and methods: Fas was over-expressed in H446/CDDP cells by infection with the adenoviruses containing Fas. Sensitivity of Fas-overexpressed H446/CDDP cells to cisplatin was evaluated using MTT assay. Expressions of Fas, GST-pi and ERCC1 were detected by RT-PCR and Western blot analysis. Apoptosis rate was examined by FACS.

Results: Over-expression of Fas in H446/CDDP cells significantly decreased the expressions of GST-pi and ERCC1 at mRNA and protein levels, and increased the cell apoptosis. Furthermore, up-regulation of Fas significantly decreased the tolerance of H446/CDDP cells to cisplatin.

Conclusion: Over-expression of Fas reverses drug resistance of H446/CDDP cells, possibly due to the increased cell sensitivity to apoptosis and the decreased expressions of GST-pi and ERCC1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • Cell Separation
  • Cisplatin / pharmacology*
  • DNA-Binding Proteins / biosynthesis
  • Drug Resistance, Multiple*
  • Drug Resistance, Neoplasm*
  • Endonucleases / biosynthesis
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Glutathione S-Transferase pi / biosynthesis
  • Humans
  • Lung Neoplasms / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Small Cell Lung Carcinoma / metabolism*
  • fas Receptor / biosynthesis*

Substances

  • Antineoplastic Agents
  • DNA-Binding Proteins
  • fas Receptor
  • Glutathione S-Transferase pi
  • ERCC1 protein, human
  • Endonucleases
  • Cisplatin