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.

• Authors: Qingxin Cao, Wuguang Lu, Tingting Zhou, Yu Liu, Xueting Cai, Jin Zhu, Peng Cao
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 455 Issue 1-2 Pg. 119-125 (May 2019) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 30535530 (Publication Type: Journal Article)

Chemical References

• 2-amino-6-chloro-alpha-cyano-3-(ethoxycarbonyl)-4H-1-benzopyran-4-acetic acid ethyl ester
• Acetates
• Analgesics
• Antineoplastic Agents
• Benzopyrans
• Peptides
• Proto-Oncogene Proteins c-akt

Topics

• Acetates (pharmacology)
• Analgesics (pharmacology)
• Animals
• Antineoplastic Agents (pharmacology)
• Benzopyrans (pharmacology)
• Carcinoma, Hepatocellular (blood supply, drug therapy, enzymology, pathology)
• Enzyme Activation (drug effects)
• Hep G2 Cells
• Human Umbilical Vein Endothelial Cells (enzymology, pathology)
• Humans
• Liver Neoplasms (blood supply, drug therapy, enzymology, pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neovascularization, Pathologic (drug therapy, enzymology, pathology)
• Peptides (pharmacokinetics)
• Proto-Oncogene Proteins c-akt (metabolism)