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Analgesic-antitumor peptide inhibits angiogenesis by suppressing AKT activation in hepatocellular carcinoma.

Abstract：

:Hepatocellular carcinoma (HCC) is one of leading causes of cancer-related death, and its increasing incidence worldwide is a cause for concern. The recombinant analgesic-antitumor peptide (rAGAP), a protein consisting of small ubiquitin-related modifier linked with a hexa-histidine tag, exhibited the antitumor activity in HepG2 tumors in our previous study. However, the underlying molecular mechanism of its antitumor activity was still elusive. In this work, we found that treatment with rAGAP reduced phosphorylation of AKT at non-toxic doses in HepG2 cells in vitro. More importantly, treatment of HepG2 cells with rAGAP downregulated protein expression of HIF-1α, suppressed activities of HIF, reduced secretion of VEGF and IL-8, and suppressed HepG2-induced tube formation by HUVEC, which was reversed by co-incubation with SC-79 (an AKT activator). Furthermore, in tumors of athymic mice with HepG2, treatment with rAGAP reduced phosphorylation of AKT, downregulated protein expression of HIF-1α and VEGF, and microvessel density marked by positive CD31 staining. Collectively, rAGAP inhibited angiogenesis by suppressing AKT activation, which partly explained its antitumor activity in HCC.

journal_name

Mol Cell Biochem

journal_title

Molecular and cellular biochemistry

authors

Cao Q,Lu W,Zhou T,Liu Y,Cai X,Zhu J,Cao P

doi

10.1007/s11010-018-3475-9

subject

Has Abstract

pub_date

2019-05-01 00:00:00

pages

119-125

issue

1-2

eissn

0300-8177

issn

1573-4919

pii

10.1007/s11010-018-3475-9

journal_volume

455

pub_type

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