Induction of apoptosis and activation of the caspase cascade by anti-EGF receptor monoclonal antibodies in DiFi human colon cancer cells do not involve the c-jun N-terminal kinase activity.
Induction of apoptosis and activation of the caspase cascade by anti-EGF receptor monoclonal antibodies in DiFi human colon cancer cells do not involve the c-jun N-terminal kinase activity.
复制标题
抗EGF受体单克隆抗体在DIFI人类结肠癌细胞中诱导凋亡和激活caspase cascade不涉及C-JUN N末端激酶活性。
DOI：
10.1054/bjoc.2000.1201
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发表时间：
2000-06
影响因子：
8.8
通讯作者：
Fan Z
中科院分区：
文献类型：
--
作者：
Liu B;Fang M;Schmidt M;Lu Y;Mendelsohn J;Fan Z
我们之前报道了DiFi人结肠癌细胞暴露于抗表皮生长因子（EGF）受体单克隆抗体（mAb） 225导致细胞凋亡，但其机制仍有待阐明。在本研究中，我们研究了一组四种抗EGF受体单克隆抗体对诱导凋亡的影响，每种单克隆抗体都与DiFi细胞中EGF受体的不同表位结合。我们发现这些单克隆抗体都能诱导DiFi细胞凋亡。暴露于mAb 225的DiFi细胞激活了起始caspase-8，在细胞暴露于抗体后8至16小时可检测到caspase-8。起始caspase-9的激活也比caspase-8的激活晚了几个小时。暴露于mAb 225的DiFi细胞也激活了执行caspase-3，这伴随着一种已被充分表征的caspase-3底物，聚(ADP)-核糖聚合酶（PARP）的切割。预先暴露于caspase-3特异性抑制剂DEVD-CHO的细胞部分减少了单抗225诱导的PARP切割和凋亡，而预先暴露于caspase泛抑制剂z-VAD-fmk的细胞完全抑制了单抗225诱导的凋亡。caspase -3、-8和-9在mAb 225仅诱导细胞周期G1期阻滞的细胞系中未被激活。与紫外线照射强烈激活c- jun n -末端激酶-1 （JNK1）和caspase级联的DiFi细胞凋亡相比，mAb 225诱导的DiFi细胞凋亡和caspase级联的激活与JNK1的激活无关。©2000癌症研究运动
We previously reported that exposure of DiFi human colon cancer cells to the anti-epidermal growth factor (EGF) receptor monoclonal antibody (mAb) 225 resulted in apoptosis, but the mechanisms remain to be elucidated. In the present study, we investigated the effects of a panel of four anti-EGF receptor mAbs, each of which binds to different epitopes of the EGF receptor in DiFi cells, on the induction of apoptosis. We found that each of these mAbs induced apoptosis in DiFi cells. Exposure of DiFi cells to mAb 225 activated the initiation caspase-8, which was detectable between 8 and 16 h after exposure of the cells to the antibody. There was also an activation of the initiation caspase-9, which lagged a few hours behind the activation of caspase-8. Exposure of DiFi cells to mAb 225 also activated the execution caspase-3, which was accompanied temporally by evidence of cleavage of a well-characterized caspase-3 substrate, poly(ADP)-ribosepolymerase (PARP). Pre-exposure of the cells to the caspase-3-specific inhibitor DEVD-CHO partially reduced the mAb 225-induced PARP cleavage and apoptosis, whereas pre-exposure of the cells to the caspase pan-inhibitor z-VAD-fmk completely inhibited mAb 225-induced apoptosis. Caspases-3, -8 and -9 were not activated in the cell lines in which mAb 225 only induced G1 phase arrest of the cell cycle. In contrast to the apoptosis of DiFi cells induced by ultraviolet irradiation, which strongly activated the c- jun N-terminal kinase-1 (JNK1) and the caspase cascade, mAb 225-induced apoptosis and activation of the caspase cascade in DiFi cells were not associated with activation of JNK1. © 2000 Cancer Research Campaign