Protein kinase C-dependent anti-apoptotic mechanism that is associated with high sensitivity to anti-Fas antibody in ovarian cancer cell lines
Protein kinase C-dependent anti-apoptotic mechanism that is associated with high sensitivity to anti-Fas antibody in ovarian cancer cell lines
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DOI：
10.1016/s0304-3835(99)00062-2
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发表时间：
1999-06-01
期刊：
影响因子：
9.7
通讯作者：
Nakashima, I
中科院分区：
文献类型：
--
作者：
Hayakawa, A;Yokoyama, I;Nakashima, I
我们比较了两个人卵巢癌细胞系，NOS 4和SKOV-3，这两个细胞表面上强烈表达Fas抗原，通过抗Fas抗体凋亡的敏感性。抗Fas抗体处理可诱导NOS 4细胞大量DNA断裂，但对SKOV-3细胞无诱导作用。然;这两种细胞系均响应钙离子载体A23187或鞘磷脂酶而发生凋亡，表明后一种细胞系能够进行DNA片段化。用PKC激活剂PMA处理两种细胞系均未诱导DNA片段化，但用蛋白激酶C（PKC）抑制剂H-7处理可诱导NOS 4细胞广泛的DNA片段化，但在SKOV-3细胞中也未诱导。蛋白激酶A抑制剂HA 1004处理在两种细胞系中均不诱导DNA片段化。相应地，在抗Fas抗体或A23187处理之前用PMA处理细胞部分抑制了NOS 4细胞中DNA片段化的诱导，但在SKOV-3细胞中不抑制。NOS 4和SKOV-3细胞株表达PKC同工酶的水平相当。这些结果表明，在这些卵巢癌细胞系中存在PKC依赖的抗凋亡机制与抗Fas抗体的高敏感性相关。(C)1999爱思唯尔科学爱尔兰有限公司保留所有权利。
We compared the sensitivities to apoptosis via anti-Fas antibody of two human ovarian cancer cell lines, NOS4 and SKOV-3, both of which strongly express the Fas antigen on their cell surface. Treatment with anti-Fas antibody induced extensive DNA fragmentation in NOS4 cells but none in SKOV-3 cells. However; both cell lines underwent apoptosis in response to calcium ionophore A23187 or sphingomyelinase, demonstrating that the latter cell line is capable of DNA fragmentation. DNA fragmentation was not induced in either cell line by treatment with PKC activator PMA, however treatment with protein kinase C (PKC) inhibitor H-7 induced extensive DNA fragmentation in NOS4 cells, but again none in SKOV-3 cells. Protein kinase A inhibitor HA1004 treatment did not induce DNA fragmentation in either cell line. Correspondingly, treatment of cells with PMA before anti-Fas antibody or A23187 treatment partially inhibited induction of DNA fragmentation in NOS4 cells but not in SKOV-3 cells. Both NOS4 and SKOV-3 cell lines expressed isozymes of PKC at comparable levels. These results suggest the presence of a PKC-dependent anti-apoptotic mechanism in association with high sensitivity to anti-Fas antibody in these ovarian cancer cell lines. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.