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Inhibition of MMP-2 Expression Enhances the Antitumor Effect of Sorafenib in Hepatocellular Carcinoma by Suppressing the PI3K/AKT/mTOR Pathway

Sorafenib has been globally approved as the standard treatment for patients with advanced hepatocellular carcinoma (HCC). However, the response rate of HCC patients to sorafenib is limited because of tumor recurrence and metastasis. Therefore, seeking combined therapeutic strategies with sorafenib i...

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Autores principales: Tan, Wenliang, Zhu, Sicong, Cao, Jun, Zhang, Lei, Li, Wenda, Liu, Kairui, Zhong, Jinyi, Shang, Changzhen, Chen, Yajin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cognizant Communication Corporation 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841021/
https://www.ncbi.nlm.nih.gov/pubmed/28276313
http://dx.doi.org/10.3727/096504017X14886444100783
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author Tan, Wenliang
Zhu, Sicong
Cao, Jun
Zhang, Lei
Li, Wenda
Liu, Kairui
Zhong, Jinyi
Shang, Changzhen
Chen, Yajin
author_facet Tan, Wenliang
Zhu, Sicong
Cao, Jun
Zhang, Lei
Li, Wenda
Liu, Kairui
Zhong, Jinyi
Shang, Changzhen
Chen, Yajin
author_sort Tan, Wenliang
collection PubMed
description Sorafenib has been globally approved as the standard treatment for patients with advanced hepatocellular carcinoma (HCC). However, the response rate of HCC patients to sorafenib is limited because of tumor recurrence and metastasis. Therefore, seeking combined therapeutic strategies with sorafenib is necessary to improve the antitumor efficiency. Here we demonstrated that expression of MMP-2 is positively correlated with the migration ability of HCC cells. Cells with a higher MMP-2 expression (SK-HEP-1 cells) were less sensitive to sorafenib than those with lower MMP-2 expression (HepG2 cells). Cotreatment of cells with SB-3CT and sorafenib more strongly inhibited migration ability than with sorafenib treatment alone in both HCC cells with high and low expression of MMP-2. In vivo cell metastasis experiments confirmed the synergistic effects of sorafenib and SB-3CT in reducing lung metastasis of SK-HEP-1 cells. Mechanistically, we showed that the synergistic antitumor effect may be attributed to inhibition of the PI3K/AKT/mTOR signaling pathway, but not the RAF/MEK/ERK signaling pathway. With these results taken together, the current study demonstrates that inhibiting MMP-2 expression can enhance the antitumor effect of sorafenib in HCC cells with a high MMP-2 expression, which may provide a novel strategy to improve therapeutic efficiency in HCC.
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spelling pubmed-78410212021-02-16 Inhibition of MMP-2 Expression Enhances the Antitumor Effect of Sorafenib in Hepatocellular Carcinoma by Suppressing the PI3K/AKT/mTOR Pathway Tan, Wenliang Zhu, Sicong Cao, Jun Zhang, Lei Li, Wenda Liu, Kairui Zhong, Jinyi Shang, Changzhen Chen, Yajin Oncol Res Article Sorafenib has been globally approved as the standard treatment for patients with advanced hepatocellular carcinoma (HCC). However, the response rate of HCC patients to sorafenib is limited because of tumor recurrence and metastasis. Therefore, seeking combined therapeutic strategies with sorafenib is necessary to improve the antitumor efficiency. Here we demonstrated that expression of MMP-2 is positively correlated with the migration ability of HCC cells. Cells with a higher MMP-2 expression (SK-HEP-1 cells) were less sensitive to sorafenib than those with lower MMP-2 expression (HepG2 cells). Cotreatment of cells with SB-3CT and sorafenib more strongly inhibited migration ability than with sorafenib treatment alone in both HCC cells with high and low expression of MMP-2. In vivo cell metastasis experiments confirmed the synergistic effects of sorafenib and SB-3CT in reducing lung metastasis of SK-HEP-1 cells. Mechanistically, we showed that the synergistic antitumor effect may be attributed to inhibition of the PI3K/AKT/mTOR signaling pathway, but not the RAF/MEK/ERK signaling pathway. With these results taken together, the current study demonstrates that inhibiting MMP-2 expression can enhance the antitumor effect of sorafenib in HCC cells with a high MMP-2 expression, which may provide a novel strategy to improve therapeutic efficiency in HCC. Cognizant Communication Corporation 2017-11-02 /pmc/articles/PMC7841021/ /pubmed/28276313 http://dx.doi.org/10.3727/096504017X14886444100783 Text en Copyright © 2017 Cognizant, LLC. http://creativecommons.org/licenses/by-nc-nd/4.0/ This article is licensed under a Creative Commons Attribution-NonCommercial NoDerivatives 4.0 International License.
spellingShingle Article
Tan, Wenliang
Zhu, Sicong
Cao, Jun
Zhang, Lei
Li, Wenda
Liu, Kairui
Zhong, Jinyi
Shang, Changzhen
Chen, Yajin
Inhibition of MMP-2 Expression Enhances the Antitumor Effect of Sorafenib in Hepatocellular Carcinoma by Suppressing the PI3K/AKT/mTOR Pathway
title Inhibition of MMP-2 Expression Enhances the Antitumor Effect of Sorafenib in Hepatocellular Carcinoma by Suppressing the PI3K/AKT/mTOR Pathway
title_full Inhibition of MMP-2 Expression Enhances the Antitumor Effect of Sorafenib in Hepatocellular Carcinoma by Suppressing the PI3K/AKT/mTOR Pathway
title_fullStr Inhibition of MMP-2 Expression Enhances the Antitumor Effect of Sorafenib in Hepatocellular Carcinoma by Suppressing the PI3K/AKT/mTOR Pathway
title_full_unstemmed Inhibition of MMP-2 Expression Enhances the Antitumor Effect of Sorafenib in Hepatocellular Carcinoma by Suppressing the PI3K/AKT/mTOR Pathway
title_short Inhibition of MMP-2 Expression Enhances the Antitumor Effect of Sorafenib in Hepatocellular Carcinoma by Suppressing the PI3K/AKT/mTOR Pathway
title_sort inhibition of mmp-2 expression enhances the antitumor effect of sorafenib in hepatocellular carcinoma by suppressing the pi3k/akt/mtor pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841021/
https://www.ncbi.nlm.nih.gov/pubmed/28276313
http://dx.doi.org/10.3727/096504017X14886444100783
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