HYD-PEP06 suppresses hepatocellular carcinoma metastasis, epithelial–mesenchymal transition and cancer stem cell-like properties by inhibiting PI3K/AKT and WNT/β-catenin signaling activation

Wei Tian; Jiatong Li; Zhuo Wang; Tong Zhang; Ying Han; Yanyan Liu; Wenfeng Chu; Yu Liu; Baofeng Yang

Acta Pharmaceutica Sinica B (Jun 2021)

HYD-PEP06 suppresses hepatocellular carcinoma metastasis, epithelial–mesenchymal transition and cancer stem cell-like properties by inhibiting PI3K/AKT and WNT/β-catenin signaling activation

Wei Tian,
Jiatong Li,
Zhuo Wang,
Tong Zhang,
Ying Han,
Yanyan Liu,
Wenfeng Chu,
Yu Liu,
Baofeng Yang

Affiliations

Wei Tian: Department of Pharmacology (the State-Province Key Laboratories of Biomedicine Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, China
Jiatong Li: Department of Pharmacology (the State-Province Key Laboratories of Biomedicine Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, China
Zhuo Wang: Department of Pharmacology (the State-Province Key Laboratories of Biomedicine Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, China
Tong Zhang: The First Affiliated Hospital of Harbin Medical University, Harbin 150081, China
Ying Han: Department of Pharmacology (the State-Province Key Laboratories of Biomedicine Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, China
Yanyan Liu: Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin 150081, China
Wenfeng Chu: Department of Pharmacology (the State-Province Key Laboratories of Biomedicine Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, China
Yu Liu: Department of Pharmacology (the State-Province Key Laboratories of Biomedicine Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, China; Corresponding authors. Tel.: +86 451 86671354; fax: +86 451 86675769.
Baofeng Yang: Department of Pharmacology (the State-Province Key Laboratories of Biomedicine Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, China; Corresponding authors. Tel.: +86 451 86671354; fax: +86 451 86675769.

Journal volume & issue: Vol. 11, no. 6
pp. 1592 – 1606

Abstract

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HYD-PEP06, an endostatin-modified polypeptide, has been shown to produce effective anti-colorectal carcinoma effects through inhibiting epithelial–mesenchymal transition (EMT). However, whether HYD-PEP06 has similar suppressive effect on hepatocellular carcinoma (HCC) remained unknown. In this study, HYD-PEP06 inhibited metastasis and EMT but not proliferation in vitro. Cignal finder pathway reporter array and Western blot analysis revealed that HYD-PEP06 suppressed HCCLM3 cell metastasis and EMT by inhibiting the PI3K/AKT pathway. Moreover, HYD-PEP06 exerted anti-metastasis effects in HepG2 cancer stem-like cells (CSCs) via suppressing the WNT/β-catenin signaling pathway. Finally, in HCCLM3 tumor-bearing BALB/c nu/nu nude mice, HYD-PEP06 substantially suppressed tumor growth, lung metastasis and HCC progress. Our results suggest that HYD-PEP06 inhibits the metastasis and EMT of HCC and CSCs as well, and thus has the potential as an agent for HCC treatment.

Published in Acta Pharmaceutica Sinica B

ISSN: 2211-3835 (Print); 2211-3843 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://www.journals.elsevier.com/acta-pharmaceutica-sinica-b

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