Enhanced susceptibility of oral squamous cell carcinoma cell lines to Fas-mediated apoptosis by cisplatin and 5-fluorouracil (Publication with Expression of Concern. See vol. 150, 2022) (Retracted article. See MAR, 2023)
Enhanced susceptibility of oral squamous cell carcinoma cell lines to Fas-mediated apoptosis by cisplatin and 5-fluorouracil (Publication with Expression of Concern. See vol. 150, 2022) (Retracted article. See MAR, 2023)
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DOI：
10.1002/ijc.11239
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发表时间：
2003-09-10
影响因子：
6.4
通讯作者：
Nagumo, M
中科院分区：
文献类型：
--
作者：
Iwase, M;Watanabe, H;Nagumo, M
本研究旨在探讨抗癌药物顺铂（cisplatin，CDDP）和5-氟尿嘧啶（5-fluorouracil，5-FU）对Fas介导的口腔鳞状细胞癌（oral squamous cell carcinoma，OSCC）细胞凋亡的影响。CDDP和/或5-FU处理OSCC细胞系NA和HSC-4后，细胞膜Fas及其mRNA表达增强。然后通过加入激动性抗Fas抗体CH-II观察到胱天蛋白酶-3和-8活性的增加。CH-II能显著增强经抗癌药物处理的OSCC细胞的凋亡，而未经处理的OSCC细胞几乎不发生凋亡。此外，CDDP和5-FU的组合导致对凋亡的敏感性增加。Caspase-3和-8抑制剂，但不是caspase-9抑制剂，减少Fas介导的细胞凋亡增强的抗癌药物。此外，用抗癌药物处理的OSCC细胞表现出细胞FADD样白细胞介素I转化酶抑制蛋白（c-FLIP）水平降低，而Fas相关的死亡结构域蛋白（FADD）和半胱氨酸天冬氨酸蛋白酶原-8的表达都没有改变。此外，c-FLIP的反义寡核苷酸证实，下调c-FLIP诱导Fas介导的凋亡的敏化。这些结果表明，CDDP和5-FU可能通过下调c-FLIP增强Fas介导的凋亡的易感性。从这些发现中，可能会开发一种新的潜在策略来提高抗癌药物的疗效。(C)2003 Wiley-Liss，Inc.
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.