Ventilagolin Suppresses Migration, Invasion and Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma Cells by Downregulating Pim-1

Ying Liu,1,2,&ast; Dao-Hai Cheng,3,&ast; Ke-Dao Lai,1 Hua Su,1 Guo-Shou Lu,1 Li Wang,1 Ji-Hua Lv1 1Department of Pharmacology, Guangxi Institute of Chinese Medicine & Pharmaceutical Science, Nanning, 530022, People’s Republic of China; 2Guangxi Key Laboratory of Traditional Chinese Medic...

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Autores principales:	Liu Y, Cheng DH, Lai KD, Su H, Lu GS, Wang L, Lv JH
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	ventilagolin pim-1 hepatocellular carcinoma epithelial-mesenchymal transition Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/a8ee36073c344e5e9c0a90be2253e1b1
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spelling	oai:doaj.org-article:a8ee36073c344e5e9c0a90be2253e1b12021-11-30T18:50:36ZVentilagolin Suppresses Migration, Invasion and Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma Cells by Downregulating Pim-11177-8881https://doaj.org/article/a8ee36073c344e5e9c0a90be2253e1b12021-12-01T00:00:00Zhttps://www.dovepress.com/ventilagolin-suppresses-migration-invasion-and-epithelial-mesenchymal--peer-reviewed-fulltext-article-DDDThttps://doaj.org/toc/1177-8881Ying Liu,1,2,&ast; Dao-Hai Cheng,3,&ast; Ke-Dao Lai,1 Hua Su,1 Guo-Shou Lu,1 Li Wang,1 Ji-Hua Lv1 1Department of Pharmacology, Guangxi Institute of Chinese Medicine & Pharmaceutical Science, Nanning, 530022, People’s Republic of China; 2Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards, Nanning, 530022, People’s Republic of China; 3Department of Pharmacy, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Liu; Ke-Dao Lai Email shenghuakai_1997@163.com; laikedao@163.comObjective: Inhibition of tumor metastasis is a useful strategy to improve the efficacy of cancer therapy. Ventilagolin, a natural 1, 4-naphthoquinone derivative extracted from Ventilago leiocarpa Benth, has shown promising antitumor effects in previous studies. However, the effects and underlying mechanisms of Ventilagolin against migration, invasion and epithelial-mesenchymal transition (EMT) of hepatocellular carcinoma (HCC) remain unclear. The present study has examined these effects and determined whether the proto-oncogene Pim-1 is involved.Methods: The effects of Ventilagolin on migration, invasion, Pim-1 and EMT-related proteins (eg, E-cadherin, N-cadherin, Vimentin) expression were assessed by scratch wound healing, Transwell, qRT-PCR and Western blot assays, respectively. Pim-1 stably overexpressed HepG2 and SMMC-7721 cells were generated to explore whether Ventilagolin inhibited migration, invasion and EMT of HCC cells via regulating Pim-1. Subcutaneous xenograft tumor model in nude mice was established. Histopathological changes of tumor tissues were examined by H&E staining and expressions of Pim-1 and EMT-related proteins were detected by immunohistochemistry.Results: Ventilagolin significantly (P < 0.01) reduced the expression of Pim-1 levels in HepG2 and SMMC-7721 cells. Compared with the control group, the migration and invasion abilities of Pim-1-overexpressing HepG2 and SMMC-7721 cells were significantly (P < 0.05, P < 0.01) enhanced, the expression of E-cadherin was decreased (P < 0.01), and the levels of N-cadherin and Vimentin were upregulated (P < 0.05, P < 0.01). Ventilagolin treatment effectively reversed these effects of Pim-1 overexpression. In vivo experiments showed that Ventilagolin could effectively suppress HCC tumor growth, downregulate Pim-1, N-cadherin and Vimentin expression, and upregulate E-cadherin expression.Conclusion: Ventilagolin suppresses HCC cell proliferation, migration and invasion and reverses EMT process by downregulating Pim-1, suggesting Ventilagolin is a potential therapeutic agent for treatment of HCC.Keywords: Ventilagolin, Pim-1, hepatocellular carcinoma, epithelial-mesenchymal transitionLiu YCheng DHLai KDSu HLu GSWang LLv JHDove Medical Pressarticleventilagolinpim-1hepatocellular carcinomaepithelial-mesenchymal transitionTherapeutics. PharmacologyRM1-950ENDrug Design, Development and Therapy, Vol Volume 15, Pp 4885-4899 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ventilagolin pim-1 hepatocellular carcinoma epithelial-mesenchymal transition Therapeutics. Pharmacology RM1-950
spellingShingle	ventilagolin pim-1 hepatocellular carcinoma epithelial-mesenchymal transition Therapeutics. Pharmacology RM1-950 Liu Y Cheng DH Lai KD Su H Lu GS Wang L Lv JH Ventilagolin Suppresses Migration, Invasion and Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma Cells by Downregulating Pim-1
description	Ying Liu,1,2,&ast; Dao-Hai Cheng,3,&ast; Ke-Dao Lai,1 Hua Su,1 Guo-Shou Lu,1 Li Wang,1 Ji-Hua Lv1 1Department of Pharmacology, Guangxi Institute of Chinese Medicine & Pharmaceutical Science, Nanning, 530022, People’s Republic of China; 2Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards, Nanning, 530022, People’s Republic of China; 3Department of Pharmacy, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Liu; Ke-Dao Lai Email shenghuakai_1997@163.com; laikedao@163.comObjective: Inhibition of tumor metastasis is a useful strategy to improve the efficacy of cancer therapy. Ventilagolin, a natural 1, 4-naphthoquinone derivative extracted from Ventilago leiocarpa Benth, has shown promising antitumor effects in previous studies. However, the effects and underlying mechanisms of Ventilagolin against migration, invasion and epithelial-mesenchymal transition (EMT) of hepatocellular carcinoma (HCC) remain unclear. The present study has examined these effects and determined whether the proto-oncogene Pim-1 is involved.Methods: The effects of Ventilagolin on migration, invasion, Pim-1 and EMT-related proteins (eg, E-cadherin, N-cadherin, Vimentin) expression were assessed by scratch wound healing, Transwell, qRT-PCR and Western blot assays, respectively. Pim-1 stably overexpressed HepG2 and SMMC-7721 cells were generated to explore whether Ventilagolin inhibited migration, invasion and EMT of HCC cells via regulating Pim-1. Subcutaneous xenograft tumor model in nude mice was established. Histopathological changes of tumor tissues were examined by H&E staining and expressions of Pim-1 and EMT-related proteins were detected by immunohistochemistry.Results: Ventilagolin significantly (P < 0.01) reduced the expression of Pim-1 levels in HepG2 and SMMC-7721 cells. Compared with the control group, the migration and invasion abilities of Pim-1-overexpressing HepG2 and SMMC-7721 cells were significantly (P < 0.05, P < 0.01) enhanced, the expression of E-cadherin was decreased (P < 0.01), and the levels of N-cadherin and Vimentin were upregulated (P < 0.05, P < 0.01). Ventilagolin treatment effectively reversed these effects of Pim-1 overexpression. In vivo experiments showed that Ventilagolin could effectively suppress HCC tumor growth, downregulate Pim-1, N-cadherin and Vimentin expression, and upregulate E-cadherin expression.Conclusion: Ventilagolin suppresses HCC cell proliferation, migration and invasion and reverses EMT process by downregulating Pim-1, suggesting Ventilagolin is a potential therapeutic agent for treatment of HCC.Keywords: Ventilagolin, Pim-1, hepatocellular carcinoma, epithelial-mesenchymal transition
format	article
author	Liu Y Cheng DH Lai KD Su H Lu GS Wang L Lv JH
author_facet	Liu Y Cheng DH Lai KD Su H Lu GS Wang L Lv JH
author_sort	Liu Y
title	Ventilagolin Suppresses Migration, Invasion and Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma Cells by Downregulating Pim-1
title_short	Ventilagolin Suppresses Migration, Invasion and Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma Cells by Downregulating Pim-1
title_full	Ventilagolin Suppresses Migration, Invasion and Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma Cells by Downregulating Pim-1
title_fullStr	Ventilagolin Suppresses Migration, Invasion and Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma Cells by Downregulating Pim-1
title_full_unstemmed	Ventilagolin Suppresses Migration, Invasion and Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma Cells by Downregulating Pim-1
title_sort	ventilagolin suppresses migration, invasion and epithelial-mesenchymal transition of hepatocellular carcinoma cells by downregulating pim-1
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/a8ee36073c344e5e9c0a90be2253e1b1
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Ventilagolin Suppresses Migration, Invasion and Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma Cells by Downregulating Pim-1

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