Notch1 regulates the JNK signaling pathway and increases apoptosis in hepatocellular carcinoma.

Notch1 regulates the JNK signaling pathway and increases apoptosis in hepatocellular carcinoma.
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DOI:
10.18632/oncotarget.17434
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发表时间:
2017-07-11
期刊:
影响因子:
--
通讯作者:
Song L
Song L
中科院分区:
其他
文献类型:
--
作者:
Sui C;Zhuang C;Sun D;Yang L;Zhang L;Song L

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在许多癌症中,NOTCH1诱导的信号通路参与细胞的生长、凋亡、运动和侵袭。在本研究中,采用体外检测方法检测了Notch1和NICD1在肝细胞癌组织中的表达。然后,我们使用Notch1 siRNA或质粒来探索细胞生物学和信号通路。在此,Notch1和NICD1在肝癌组织中的表达显著降低。在体外,Notch1质粒抑制细胞的增殖、迁移和侵袭,但促进细胞的凋亡。相反,si-Notch1促进了细胞的增殖、迁移和侵袭,但抑制了细胞的凋亡。Notch1机械作用于HepG2和Hep3B细胞,降低了细胞周期蛋白D1、基质金属蛋白酶-9和Bcl-2的表达,而上调了p-JNK、Bax和裂解的caspase 3的表达。此外,si-JNK或JNK抑制剂SP600125影响Notch1信号通路的激活,阻止细胞凋亡。综上所述,Notch1调控JNK信号通路,促进肝癌细胞的凋亡。由于肝细胞癌患者预后较差,Notch1通路可能提供一种新的治疗策略。
Notch1-induced pathways are involved in cell growth, apoptosis, motility, and invasion in many cancers. In the present study, the expression of Notch1 and NICD1 was detected in hepatocellular carcinoma (HCC) tissues using in-vitro assays. And then, we explored cell biology and signaling pathways using Notch1 siRNA or plasmids. Here, the expression of Notch1 and NICD1 was significantly decreased in HCC tissues. In-vitro, Notch1 plasmids inhibited cell proliferation, migration and invasion, but enhanced apoptosis of HepG2 and Hep3B cells. Conversely, si-Notch1 enhanced cell proliferation, migration and invasion, but inhibited apoptosis of HepG2 and Hep3B cells. Mechanically, Notch1 decreased the expression of cyclin D1, MMP-9 and Bcl-2, but increased the expression of p-JNK, Bax and cleaved caspase 3 in HepG2 and Hep3B cells. Besides, si-JNK or JNK inhibitor SP600125 affected the activation of Notch1 signaling pathway, and prevents cell apoptosis. In conclusion, Notch1 regulates the JNK signaling pathway and increases apoptosis in HCC. Because patients with HCC have a poor prognosis, Notch1 pathway may provide a novel treatment strategy.
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