Anticancer drug-Induced Fas (CD95)-dependent Apoptosis of Human Tongue Carcinoma

我们通过观察舌癌的细胞凋亡和抗癌药物的作用，发现在舌癌中介导细胞凋亡级联反应的分子。卡铂（CBDCA）、培霉素和甲氨蝶呤可诱导人高分化舌鳞癌SCC-25细胞凋亡。中和的抗fas和抗fas配体（FasL）抗体消除了cbdca诱导的细胞死亡，通过DNA片段测量和相衬显微镜观察进行了检测。在缺乏CBDCA的情况下，与细胞表面Fas结合并激活Fas的细胞毒性抗Fas抗体未能诱导细胞凋亡。然而，细胞毒性抗体以剂量依赖的方式显著增强cbdca诱导的细胞凋亡。Western blotting和反转录PCR显示，CBDCA处理后，Fas和FasL的表达没有变化。SCC-25诱导fas敏感t淋巴白血病Jurkat细胞凋亡。这些结果表明，舌癌细胞表达非功能性Fas和功能性Fas配体，它们本身不能诱导细胞凋亡，CBDCA处理将非功能性Fas转换为功能性Fas，激活Fas敏感通路导致细胞凋亡。

We examined the apoptosis of tongue carcinoma and the effects of anticancer drugs to identify the molecules that mediate apoptotic cascade in the malignancy. Carboplatin (CBDCA), peplomycin and methotrexate induced apoptosis of SCC-25, human well-differentiated tongue squamous carcinoma cell line, as detected by measurement of DNA fragmentation. Neutralizing anti-Fas and anti-Fas ligand (FasL) antibodies obliterated the CBDCA-induced cell death, examined by both measurement of DNA fragmentation and phase-contrast microscopic observation. In the absence of CBDCA, cytotoxic anti-Fas antibody, which binds to and activates Fas at the cell surface, failed to induce the apoptosis. However, the cytotoxic antibody markedly enhanced the CBDCA-induced apoptosis in a dose-dependent manner.Western blotting and reverse-transcript PCR revealed that there were no alterations in Fas or FasL expression upon CBDCA treatment. SCC-25 induced apoptosis of Jurkat cells, Fas-sensitive T-lymphatic leukemia cell line. These results indicate that the tongue carcinoma cells express nonfunctional Fas and functional Fas ligand, which by themselves fail to induce apoptosis, and that CBDCA treatment switches nonfunctional Fas to functional Fas, activating a Fas sensitive pathway leading to apoptosis.