2003年9月
Enhanced susceptibility of oral squamous cell carcinoma cell lines to Fas-mediated apoptosis by cisplatin and 5-fluorouracil
INTERNATIONAL JOURNAL OF CANCER
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- 巻
- 106
- 号
- 4
- 開始ページ
- 619
- 終了ページ
- 625
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1002/ijc.11239
- 出版者・発行元
- WILEY-LISS
Our study was conducted to investigate whether anticancer drugs, cisplatin (CDDP) and/or 5-fluorouracil (5-FU), can modulate Fas-mediated apoptosis in oral squamous cell carcinoma (OSCC) cell lines. When OSCC cell lines, NA and HSC-4, were treated with CDDP and/or 5-FU, Fas and its mRNA expression on the plasma membrane were enhanced. An increase in caspase-3 and -8 activities was then observed by the addition of agonistic anti-Fas antibody, CH-II. Apoptosis of OSCC cells treated with anticancer drugs were significantly enhanced by CH-II, whereas untreated cells were nearly resistant to apoptosis. Moreover, the combination of CDDP and 5-FU resulted in an increasing susceptibility to apoptosis. Caspase-3 and -8 inhibitors, but not caspase-9 inhibitor, reduced Fas-mediated apoptosis enhanced by the anticancer drugs. Furthermore, OSCC cells treated with anticancer drugs exhibited decreased cellular FADD-like interleukin I-converting enzyme-inhibitory protein (c-FLIP) levels, whereas neither the Fas-associated death domain-containing protein (FADD) nor procaspase-8 changed the expression. Moreover, antisense oligonucleotide to c-FLIP confirmed that down-regulation of c-FLIP induced sensitization to Fas-mediated apoptosis. These results suggest that CDDP and 5-FU may enhance the susceptibility to Fas-mediated apoptosis through down-regulation of c-FLIP. From these findings, a new potential strategy may be developed to improve the efficacy of anticancer drugs. (C) 2003 Wiley-Liss, Inc.
- リンク情報
- ID情報
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- DOI : 10.1002/ijc.11239
- ISSN : 0020-7136
- Web of Science ID : WOS:000184672300025