Activation of caspase-8 is critical for sensitivity to cytotoxic anti-Fas antibody-induced apoptosis in human ovarian cancer cells
Activation of caspase-8 is critical for sensitivity to cytotoxic anti-Fas antibody-induced apoptosis in human ovarian cancer cells
复制标题
Caspase-8 的激活对于细胞毒性抗 Fas 抗体诱导的人卵巢癌细胞凋亡的敏感性至关重要
作者：
Akemi Hayakawa;Jianghong Wu;Yoshiyuki Kawamoto;Yan;Sei;Izumi Nakashima;Haruhiko Suzuki
两个卵巢癌细胞系命名为NOS4和SKOV-3已被证明具有不同的敏感性细胞毒性抗Fas抗体，CH-11。虽然这两种细胞系在细胞表面以相同的强度表达Fas分子，但CH-11在NOS 4细胞中诱导凋亡，而在SKOV-3细胞中不诱导凋亡。在这项研究中，这些细胞的不同增殖敏感性进行了评估。两种细胞系表达几乎相同水平的FADD、RIP、c-FLIP、FAP-1、Bax、Bcl-2和Bcl-XL。caspase-8，caspase-9和caspase-3的激活和切割的PARP和Bid的证据中获得的NOS 4细胞，但不是在SKOV-3细胞。当FasL蛋白触发时，SKOV-3细胞中观察到DNA断裂和caspase-8激活，但它们不如NOS 4细胞明显。Caspase-8特异性抑制剂Z-IETD-FMK可完全阻断抗Fas抗体诱导的NOS 4细胞凋亡信号。这些结果表明，抗Fas抗体的不同敏感性仅依赖于caspase-8的激活，这可能是由尚未未知的定性或定量异常的分子参与DISC形成的影响。
Two ovarian cancer cell lines named NOS4 and SKOV-3 have been shown to have different sensitivities to a cytotoxic anti-Fas antibody, CH-11. Although both cell lines express Fas molecules on the cell surfaces at the same intensities, apoptosis is induced by CH-11 in NOS4 cells but not in SKOV-3 cells. In this study, the different apoptosis-sensitivities of these cells were assessed. Both cell lines express almost the same levels of FADD, RIP, c-FLIP, FAP-1, Bax, Bcl-2 and Bcl-XL. Evidence of caspase-8, caspase-9 and caspase-3 activation and of cleavage of PARP and Bid was obtained in NOS4 cells but not in SKOV-3 cells. When triggered by FasL protein, DNA fragmentation and caspase-8 activation were observed in SKOV-3 cells, though they were not as clear as in NOS4 cells. All the anti-Fas antibody-mediated signals for apoptosis induction in NOS4 cells were completely blocked by a caspase-8-specific inhibitor, Z-IETD-FMK. These results indicate that the different sensitivities to the anti-Fas antibody are solely dependent on the activation of caspase-8, which could be influenced by yet unknown qualitative or quantitative abnormalities in molecules involved in DISC formation.
p53 依赖性 DNA 损伤诱导的细胞凋亡需要 Fas/APO-1 独立的 CPP32beta 激活。
影响因子：
11.2
作者：
Fuchs,EJ;McKenna,KA;Bedi,A
通讯作者：
Bedi,A
影响因子：
10.5
作者：
Wang, K;Yin, XM;Korsmeyer, SJ
通讯作者：
Korsmeyer, SJ
影响因子：
16
作者：
Srinivasula, SM;Ahmad, M;Alnemri, ES
通讯作者：
Alnemri, ES