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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

查看全文 作　　者：Wei [1]Tian;Jiatong [1]Li;Zhuo [1]Wang;Tong [2]Zhang;Ying [1]Han;Yanyan [3]Liu;Wenfeng [1]Chu;Yu [1]Liu;Baofeng [1]Yang 高影响力作者 机构地区：[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高影响力机构 出　　处：《Acta Pharmaceutica Sinica B》索引2021年第11卷第6期,共15页高影响力期刊 基　　金：the financial support by the National Natural Science Foundation of China (Nos. 81770281, 81730012, and 81861128022)。 摘　　要：HYD-PEP06,an endostatin-modified polypeptide,has been shown to produce effective anticolorectal 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 PI3 K/AKT pathway.Moreover,HYD-PEP06 exerted antimetastasis 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. 关 键 词：Hepatocellular carcinoma HYD-PEP06 Cancer stem-like cell PI3K/AKT WNT/Β-CATENIN
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