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Vitamin K2 Inhibits Hepatocellular Carcinoma Cell Proliferation by Binding to 17β-Hydroxysteroid Dehydrogenase 4

Our previous studies have proved that 17β-hydroxysteroid dehydrogenase 4 (HSD17B4) is a novel proliferation-promoting protein. The overexpression of HSD17B4 promotes hepatocellular carcinoma (HCC) cell proliferation. Vitamin K2 (VK2), a fat-soluble vitamin, has the function of promoting coagulation...

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Autores principales: Lu, Xin, Ma, Panpan, Kong, Lingyu, Wang, Xi, Wang, Yaqi, Jiang, Lingling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8630649/
https://www.ncbi.nlm.nih.gov/pubmed/34858832
http://dx.doi.org/10.3389/fonc.2021.757603
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author Lu, Xin
Ma, Panpan
Kong, Lingyu
Wang, Xi
Wang, Yaqi
Jiang, Lingling
author_facet Lu, Xin
Ma, Panpan
Kong, Lingyu
Wang, Xi
Wang, Yaqi
Jiang, Lingling
author_sort Lu, Xin
collection PubMed
description Our previous studies have proved that 17β-hydroxysteroid dehydrogenase 4 (HSD17B4) is a novel proliferation-promoting protein. The overexpression of HSD17B4 promotes hepatocellular carcinoma (HCC) cell proliferation. Vitamin K2 (VK2), a fat-soluble vitamin, has the function of promoting coagulation and can inhibit the progression of liver cancer. A previous study demonstrated that VK2 could bind to HSD17B4 in HepG2 cells. However, the mechanism of VK2 in inhibiting HCC cell proliferation is not clear. In this study, we investigate whether VK2 can inhibit the proliferation of HCC cell induced by HSD17B4 and the possible mechanism. We detected the effect of VK2 on HSD17B4-induced HCC cell proliferation, and the activation of STAT3, AKT, and MEK/ERK signaling pathways. We measured the effect of HSD17B4 on the growth of transplanted tumor and the inhibitory effect of VK2. Our results indicated that VK2 directly binds to HSD17B4, but does not affect the expression of HSD17B4, to inhibit the proliferation of HCC cells by inhibiting the activation of Akt and MEK/ERK signaling pathways, leading to decreased STAT3 activation. VK2 also inhibited the growth of HSD17B4-induced transplanted tumors. These findings provide a theoretical and experimental basis for possible future prevention and treatment of HCC using VK2.
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spelling pubmed-86306492021-12-01 Vitamin K2 Inhibits Hepatocellular Carcinoma Cell Proliferation by Binding to 17β-Hydroxysteroid Dehydrogenase 4 Lu, Xin Ma, Panpan Kong, Lingyu Wang, Xi Wang, Yaqi Jiang, Lingling Front Oncol Oncology Our previous studies have proved that 17β-hydroxysteroid dehydrogenase 4 (HSD17B4) is a novel proliferation-promoting protein. The overexpression of HSD17B4 promotes hepatocellular carcinoma (HCC) cell proliferation. Vitamin K2 (VK2), a fat-soluble vitamin, has the function of promoting coagulation and can inhibit the progression of liver cancer. A previous study demonstrated that VK2 could bind to HSD17B4 in HepG2 cells. However, the mechanism of VK2 in inhibiting HCC cell proliferation is not clear. In this study, we investigate whether VK2 can inhibit the proliferation of HCC cell induced by HSD17B4 and the possible mechanism. We detected the effect of VK2 on HSD17B4-induced HCC cell proliferation, and the activation of STAT3, AKT, and MEK/ERK signaling pathways. We measured the effect of HSD17B4 on the growth of transplanted tumor and the inhibitory effect of VK2. Our results indicated that VK2 directly binds to HSD17B4, but does not affect the expression of HSD17B4, to inhibit the proliferation of HCC cells by inhibiting the activation of Akt and MEK/ERK signaling pathways, leading to decreased STAT3 activation. VK2 also inhibited the growth of HSD17B4-induced transplanted tumors. These findings provide a theoretical and experimental basis for possible future prevention and treatment of HCC using VK2. Frontiers Media S.A. 2021-11-09 /pmc/articles/PMC8630649/ /pubmed/34858832 http://dx.doi.org/10.3389/fonc.2021.757603 Text en Copyright © 2021 Lu, Ma, Kong, Wang, Wang and Jiang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Lu, Xin
Ma, Panpan
Kong, Lingyu
Wang, Xi
Wang, Yaqi
Jiang, Lingling
Vitamin K2 Inhibits Hepatocellular Carcinoma Cell Proliferation by Binding to 17β-Hydroxysteroid Dehydrogenase 4
title Vitamin K2 Inhibits Hepatocellular Carcinoma Cell Proliferation by Binding to 17β-Hydroxysteroid Dehydrogenase 4
title_full Vitamin K2 Inhibits Hepatocellular Carcinoma Cell Proliferation by Binding to 17β-Hydroxysteroid Dehydrogenase 4
title_fullStr Vitamin K2 Inhibits Hepatocellular Carcinoma Cell Proliferation by Binding to 17β-Hydroxysteroid Dehydrogenase 4
title_full_unstemmed Vitamin K2 Inhibits Hepatocellular Carcinoma Cell Proliferation by Binding to 17β-Hydroxysteroid Dehydrogenase 4
title_short Vitamin K2 Inhibits Hepatocellular Carcinoma Cell Proliferation by Binding to 17β-Hydroxysteroid Dehydrogenase 4
title_sort vitamin k2 inhibits hepatocellular carcinoma cell proliferation by binding to 17β-hydroxysteroid dehydrogenase 4
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8630649/
https://www.ncbi.nlm.nih.gov/pubmed/34858832
http://dx.doi.org/10.3389/fonc.2021.757603
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