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

抗癌药物诱导的Fas（CD95）依赖性人舌癌细胞凋亡

• 批准号: 10671766
• 负责人: MISHIMA Koichi
• 金额: $ 2.24万
• 依托单位: Shimane Medical University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671766/
• 关键词: apoptosis; Fas; Fas ligand; anticancer drug; tongue carcinoma; レイノイド; 細胞死

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.

我们检测了舌癌细胞凋亡和抗癌药物的作用，以确定恶性肿瘤中介导凋亡级联反应的分子。卡铂、培洛霉素和甲氨蝶呤诱导人舌高分化鳞癌细胞株SCC-25凋亡的实验研究中和抗Fas和抗Fas配体（FasL）抗体消除了CBDCA诱导的细胞死亡，通过DNA片段化的测量和相差显微镜观察来检查。在不存在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。然而，细胞毒性抗体以剂量依赖性方式显着增强CBDCA诱导的细胞凋亡。Western blotting和逆转录PCR显示，CBDCA处理后Fas或FasL表达没有改变。SCC-25诱导Jurkat细胞凋亡，Fas敏感的T淋巴白血病细胞系。这些结果表明，舌癌细胞表达非功能性Fas和功能性Fas配体，它们本身无法诱导细胞凋亡，并且CBDCA处理将非功能性Fas转换为功能性Fas，激活Fas敏感途径，导致细胞凋亡。