2. Academic Validation
  3. 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

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

  • Acta Pharm Sin B. 2021 Jun;11(6):1592-1606. doi: 10.1016/j.apsb.2021.03.040.
Wei Tian 1,  Jiatong Li 1,  Zhuo Wang 1,  Tong Zhang 2,  Ying Han 1,  Yanyan Liu 3,  Wenfeng Chu 1,  Yu Liu 1,  Baofeng Yang 1
Affiliations

Affiliations

  • 1 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.
  • 2 The First Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
  • 3 Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin 150081, China.
PMID: 34221870 DOI: 10.1016/j.apsb.2021.03.040
Abstract

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.

Keywords

Cancer stem-like cell; HYD-PEP06; Hepatocellular carcinoma; PI3K/AKT; WNT/β-catenin.

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