Involvement of JNK-mediated pathway in EGF-mediated protection against paclitaxel-induced apoptosis in SiHa human cervical cancer cells
Involvement of JNK-mediated pathway in EGF-mediated protection against paclitaxel-induced apoptosis in SiHa human cervical cancer cells
复制标题
DOI：
10.1054/bjoc.2001.1910
复制
发表时间：
2001-07-20
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;Fan, Z
我们研究了表皮生长因子（EGF）调节紫杉醇诱导的SiHa人宫颈癌细胞凋亡的信号通路。SiHa细胞暴露于紫杉醇发生凋亡，这是强烈抑制EGF。用PI-3 K特异性抑制剂LY 294002药理学阻断磷脂酰肌醇3 '-OH激酶（PI-3 K）或用促分裂原活化蛋白激酶（MAPK）激酶（MEK）阻断MEK特异性抑制剂PD 98059或通过用PI-3 K或MEK显性负表达载体转染细胞，都不会改变EGF对细胞凋亡的抑制作用。EGF没有刺激PI-3 K/Akt，MEK/MAPK，或p38 MAPK活性在SiHa细胞，但瞬时激活c-Jun氨基末端激酶（JNK）。SB 202190抑制JNK浓度的SiHa细胞共暴露取消了EGF对SiHa细胞对紫杉醇诱导的凋亡的保护作用。我们的研究结果表明，JNK信号通路在EGF介导的保护紫杉醇诱导的SiHa细胞凋亡中起着重要作用。(C)2001年癌症研究运动。
We investigated the signalling pathways by which epidermal growth factor (EGF) modulates paclitaxel-induced apoptosis in SiHa human cervical cancer cells. SiHa cells exposed to paclitaxel underwent apoptosis, which was strongly inhibited by EGF. This inhibition of apoptosis by EGF was not altered by pharmacological blockade of phosphatidylinositol 3'-OH kinase (PI-3K) with the PI-3K specific inhibitor LY294002 or blockade of the mitogen-activated protein kinase (MAPK) kinase (MEK) with the MEK specific inhibitor PD98059, or by transfection of the cells with PI-3K or MEK dominant-negative expression vectors. EGF did not stimulate PI-3K/Akt, MEK/MAPK, or p38 MAPK activity in SiHa cells but did transiently activate the c-Jun NH2-terminal kinase (JNK). Co-exposure of SiHa cells to SB202190 at concentrations that inhibit JNK abolished the protective effect of EGF on SiHa cells against paclitaxel-induced apoptosis. Our findings indicate that the JNK signaling pathway plays an important role in EGF-mediated protection from paclitaxel-induced apoptosis in SiHa cells. (C) 2001 Cancer Research Campaign.