Enhanced susceptibility of oral squamous cell carcinoma cell lines to FAS-mediated apoptosis by cisplatin and 5-fluorouracil

✍ Scribed by Masayasu Iwase; Hitoshi Watanabe; Gen Kondo; Masaru Ohashi; Masao Nagumo

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: French
• Weight: 263 KB
• Volume: 106
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.11239

✦ Synopsis

Abstract

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‐11. Apoptosis of OSCC cells treated with anticancer drugs were significantly enhanced by CH‐11, 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 1‐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. © 2003 Wiley‐Liss, Inc.