Melittin Inhibits Hypoxia-Induced Vasculogenic Mimicry Formation and Epithelial-Mesenchymal Transition through Suppression of HIF-1α/Akt Pathway in Liver Cancer

被引：33

作者：

Chen, Qunwei ^{[1
]}

Lin, Wanfu ^{[2
]}

Yin, Zifei ^{[2
]}

Zou, Yong ^{[2
]}

Liang, Shufang ^{[2
]}

Ruan, Shanming ^{[1
]}

Chen, Peifeng ^{[1
]}

Li, Shu ^{[3
]}

Shu, Qijin ^{[1
]}

Cheng, Binbin ^{[2
]}

Ling, Changquan ^{[2
]}

机构：

[1] Zhejiang Prov Hosp Tradit Chinese Med, Dept Oncol, Hangzhou 310006, Zhejiang, Peoples R China

[2] Second Mil Med Univ, Changhai Hosp, Dept Tradit Chinese Med, Shanghai 200433, Peoples R China

[3] Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Baoshan Branch, Dept Gastroenterol, Shanghai 201900, Peoples R China

来源：

EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE | 2019年 / 2019卷

基金：

中国国家自然科学基金;

关键词：

CARCINOMA; METASTASIS; EXPRESSION; MIGRATION; INVASION; CELLS;

D O I：

10.1155/2019/9602935

中图分类号：

R [医药、卫生];

学科分类号：

10 ;

摘要：

In this study, we investigated whether melittin could suppress hypoxia-induced vasculogenic mimicry (VM) formation in liver cancer and explored the underlying mechanisms. Melittin significantly inhibited the proliferation of liver cancer cells with or without CoCl2 presence. Melittin also significantly inhibited CoCl2-induced migration, invasion, and VM formation of liver cancer cells. CoCl2 treatment suppressed the expression of E-cadherin and elevated the expression of N-cadherin and Vimentin. Melittin reversed the changes in the protein and mRNA levels of these epithelial-mesenchymal transition (EMT) markers. CoCl2-induced accumulation of HIF-1 alpha increased the level of phosphorylated Akt and upregulated the expression of VEGF and MMP-2/9. Melittin decreased the HIF-1 alpha level and thereby suppressed the levels of p-Akt, VEGF, and MMP-2/9. In addition, the inhibitor of PI3K/Akt also suppressed CoCl2-induced EMT and liver cancer cells migration, and the activator of Akt, SC-79, partly blocked the effect of melittin on CoCl2-induced EMT and liver cancer cells migration. In the xenograft tumor model in nude mice, melittin treatment significantly suppressed the tumor growth, VM formation, and HIF-1 alpha expression in the tumor. In conclusion, this study indicates melittin may inhibit hypoxia-induced VM formation and EMT in liver cancer through inhibiting HIF-1 alpha/Akt pathway.

引用

页数：10

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