Anlotinib induces hepatocellular carcinoma apoptosis and inhibits proliferation via Erk and Akt pathway
Anlotinib induces hepatocellular carcinoma apoptosis and inhibits proliferation via Erk and Akt pathway
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DOI：
10.1016/j.bbrc.2018.08.098
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发表时间：
2018-09-18
影响因子：
3.1
通讯作者：
Hao, Yongqiang
中科院分区：
文献类型：
--
作者：
He, Chao;Wu, Tingting;Hao, Yongqiang
安洛替尼是一种多靶点受体酪氨酸激酶抑制剂，虽然在临床前和临床试验中已被报道具有抗肿瘤作用，但其对肝细胞癌（HCC）的作用尚不清楚。在这里，我们已经显示了安洛替尼对HCC的抗肿瘤作用。数据表明，在体外应用安洛替尼显著抑制HCC细胞活力、增殖、集落形成，并促进凋亡。此外，动物实验也表明，安洛替尼缓解HCC进展。从机制上讲，我们证明了安洛替尼治疗下调了抗凋亡蛋白Bcl-2和Survivin，但上调了促凋亡分子Bax，这是其对HCC的治疗效果。途径分析显示Erk和Akt的磷酸化水平降低。总之，这项研究表明，安洛替尼可能通过抑制Bcl-2和Survivin表达，通过灭活Erk和Akt通路促进Bax表达，对HCC具有直接的抗肿瘤进展作用，并且可能是一种有前途的治疗HCC的药物。(C)2018爱思唯尔公司All rights reserved.
Although anlotinib, a multi-targeted receptor tyrosine kinase inhibitor has been reported have antitumor effects in many preclinical and clinical trials, little is known about its effect on hepatocellular carcinoma (HCC). Here, we have shown the antitumor effects of anlotinib on HCC. Data indicated that anlotinib application significantly inhibited HCC cell viability, proliferation, colony formation, and prompted apoptosis in vitro. Furthermore, animal experiments also illustrated that anlotinib alleviated HCC progression. Mechanically, we demonstrated that anlotinib treatment downregulated the anti-apoptotic protein Bcl-2 and Survivin, but upregulated pro-apoptotic molecule Bax, which accounts for its therapeutic effect on HCC. Pathway analysis has shown decreased phosphorylation levels of Erk and Akt. Together, this study suggests that anlotinib may have a direct antitumor progression effect on HCC by inhibiting Bcl-2 and Survivin expression, promoting Bax expression via inactivating Erk and Akt pathways and could be a promising agent treating HCC. (C) 2018 Elsevier Inc. All rights reserved.