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

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.

• Authors: Wei Wu, Hai-Dong Wang, Wei Guo, Kang Yang, Yun-ping Zhao, Yao-guang Jiang, Ping He
• Journal: Journal of experimental & clinical cancer research : CR (J Exp Clin Cancer Res) Vol. 29 Pg. 49 (May 14 2010) ISSN: 1756-9966 [Electronic] England
• PMID: 20470393 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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)