In:
Evidence-Based Complementary and Alternative Medicine, Hindawi Limited, Vol. 2019 ( 2019-04-01), p. 1-10
Abstract:
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 CoCl 2 presence. Melittin also significantly inhibited CoCl 2 -induced migration, invasion, and VM formation of liver cancer cells. CoCl 2 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. CoCl 2 -induced accumulation of HIF-1 α increased the level of phosphorylated Akt and upregulated the expression of VEGF and MMP-2/9. Melittin decreased the HIF-1 α level and thereby suppressed the levels of p-Akt, VEGF, and MMP-2/9. In addition, the inhibitor of PI3K/Akt also suppressed CoCl 2 -induced EMT and liver cancer cells migration, and the activator of Akt, SC-79, partly blocked the effect of melittin on CoCl 2 -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 α 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 α /Akt pathway.
Type of Medium:
Online Resource
ISSN:
1741-427X
,
1741-4288
DOI:
10.1155/2019/9602935
Language:
English
Publisher:
Hindawi Limited
Publication Date:
2019
detail.hit.zdb_id:
2148302-4
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