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


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.


CONCLUSIONS
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.
Wu
Wei
W
Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, PR China.
Wang
Hai-Dong
HD
Guo
Wei
W
Yang
Kang
K
Zhao
Yun-ping
YP
Jiang
Yao-guang
YG
He
Ping
P
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002469:Cell Separation; D002945:Cisplatin / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004720:Endonucleases / Q000096:biosynthesis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D051549:Glutathione S-Transferase pi / Q000096:biosynthesis; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055752:Small Cell Lung Carcinoma / Q000378:metabolism*; D019014:fas Receptor / Q000096:biosynthesis*
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D019014:fas Receptor; D051549:Glutathione S-Transferase pi; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin
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