title: Up-regulation of Fas reverses cisplatin resistance of human small cell lung cancer cells.
abstract: 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.
authors.affiliation: Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Hai-Dong
authors.initials: HD
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.forename: Kang
authors.initials: K
authors.lastname: Yang
authors.forename: Yun-ping
authors.initials: YP
authors.lastname: Zhao
authors.forename: Yao-guang
authors.initials: YG
authors.lastname: Jiang
authors.forename: Ping
authors.initials: P
authors.lastname: He
mesh_terms: 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*
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D019014:fas Receptor; D051549:Glutathione S-Transferase pi; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin
references.citation: Oncogene. 2003 Oct 20;22(47):7265-79
references.pmid: 14576837
references.citation: Nature. 1996 Dec 19-26;384(6610):638-41
references.pmid: 8967952
references.citation: J Immunol. 1992 Feb 15;148(4):1274-9
references.pmid: 1371136
references.citation: Anticancer Res. 2000 Mar-Apr;20(2A):645-52
references.pmid: 10810335
references.citation: Int J Mol Med. 2004 Aug;14(2):185-9
references.pmid: 15254763
references.citation: Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10772-6
references.pmid: 1438274
references.citation: Nat Med. 1996 May;2(5):574-7
references.pmid: 8616718
references.citation: Biochem Soc Trans. 1997 May;25(2):405-10
references.pmid: 9191126
references.citation: Cancer Res. 2003 Dec 1;63(23):8097-102
references.pmid: 14678959
references.citation: Int J Oncol. 2004 Sep;25(3):721-8
references.pmid: 15289875
references.citation: Nucleic Acids Res. 2002 May 1;30(9):e36
references.pmid: 11972351
references.citation: Recent Pat Anticancer Drug Discov. 2010 Jan;5(1):22-8
references.pmid: 19663773
references.citation: Oral Oncol. 2009 Jan;45(1):69-84
references.pmid: 18620901
references.citation: Virchows Arch. 2005 Sep;447(3):626-33
references.pmid: 15968547
references.citation: Int J Cancer. 2004 Jun 20;110(3):352-61
references.pmid: 15095299
references.citation: J Natl Cancer Inst. 1997 Jun 4;89(11):783-9
references.pmid: 9182976
references.citation: Oncol Rep. 1999 Sep-Oct;6(5):979-82
references.pmid: 10425290
references.citation: Cancer Lett. 2002 Jan 10;175(1):27-38
references.pmid: 11734333
references.citation: Acta Cytol. 1998 Nov-Dec;42(6):1397-402
references.pmid: 9850649
references.citation: Cancer Treat Rev. 1998 Oct;24(5):331-44
references.pmid: 9861196
references.citation: Cancer Res. 1998 Apr 15;58(8):1741-9
references.pmid: 9563493
references.citation: Oncology. 2000 Nov;59(4):336-43
references.pmid: 11096347
references.citation: Anticancer Res. 2000 Sep- Oct;20(5B):3449-58
references.pmid: 11131647
references.citation: Surgery. 1999 Jan;125(1):73-84
references.pmid: 9889801
references.citation: Biochem Biophys Res Commun. 2005 Feb 4;327(1):225-33
references.pmid: 15629453
references.citation: Cancer Cells. 1990 Aug-Sep;2(8-9):275-80
references.pmid: 2223389
references.citation: J Clin Invest. 1994 Aug;94(2):703-8
references.pmid: 8040325
references.citation: Pharmacotherapy. 1996 Jan-Feb;16(1):16-39
references.pmid: 8700790
references.citation: J Exp Med. 1998 Dec 7;188(11):2033-45
references.pmid: 9841917
references.citation: Cancer Control. 2003 Jul-Aug;10(4):297-305
references.pmid: 12915808
references.citation: Mol Cell Biol. 1992 Sep;12(9):3689-98
references.pmid: 1380646
references.citation: J Clin Invest. 1997 Feb 1;99(3):403-13
references.pmid: 9022073
references.citation: Mol Pharmacol. 2010 Feb;77(2):298-310
references.pmid: 19910452
references.citation: Lung Cancer. 2005 Dec;50 Suppl 2:S33-40
references.pmid: 16557672
references.citation: Int J Cancer. 2001 Sep 1;93(5):725-30
references.pmid: 11477586
references.citation: Adv Immunol. 1994;57:129-44
references.pmid: 7532907
references.citation: Ai Zheng. 2004 Jul;23(7):845-50
references.pmid: 15248926
references.citation: Blood. 1997 Oct 15;90(8):3118-29
references.pmid: 9376593
references.citation: Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3497-504
references.pmid: 7909602