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

我们研究了舌癌的细胞凋亡和抗癌药物的作用，以确定在舌癌中介导细胞凋亡级联的分子。DNA片段化检测显示卡铂(CBDCA)、培普霉素和甲氨蝶呤诱导人高分化舌鳞状细胞癌细胞系SCC-25的凋亡。中和抗Fas和抗Fas配体(FasL)抗体阻断CBDCA诱导的细胞死亡，DNA片段化测量和相差显微镜观察都证实了这一点。在没有CBDCA的情况下，结合并激活细胞表面Fas的细胞毒性抗Fas抗体不能诱导细胞凋亡。免疫印迹和逆转录聚合酶链式反应显示，CBDCA处理后Fas和FasL的表达无明显变化。SCC-25可诱导Fas敏感型T淋巴细胞白血病细胞株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治疗将非功能性Fas转换为功能性Fas，激活了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.