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Resveratrol Promotes Tumor Microvessel Growth via Endoglin and Extracellular Signal-Regulated Kinase Signaling Pathway and Enhances the Anticancer Efficacy of Gemcitabine against Lung Cancer

The synergistic anticancer effect of gemcitabine (GEM) and resveratrol (RSVL) has been noted in certain cancer types. However, whether the same phenomenon would occur in lung cancer is unclear. Here, we uncovered the molecular mechanism by which RSVL enhances the anticancer effect of GEM against lun...

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Autores principales: Qin, San-Hai, Lau, Andy T. Y., Liang, Zhan-Ling, Tan, Heng Wee, Ji, Yan-Chen, Zhong, Qiu-Hua, Zhao, Xiao-Yun, Xu, Yan-Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225973/
https://www.ncbi.nlm.nih.gov/pubmed/32326402
http://dx.doi.org/10.3390/cancers12040974
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author Qin, San-Hai
Lau, Andy T. Y.
Liang, Zhan-Ling
Tan, Heng Wee
Ji, Yan-Chen
Zhong, Qiu-Hua
Zhao, Xiao-Yun
Xu, Yan-Ming
author_facet Qin, San-Hai
Lau, Andy T. Y.
Liang, Zhan-Ling
Tan, Heng Wee
Ji, Yan-Chen
Zhong, Qiu-Hua
Zhao, Xiao-Yun
Xu, Yan-Ming
author_sort Qin, San-Hai
collection PubMed
description The synergistic anticancer effect of gemcitabine (GEM) and resveratrol (RSVL) has been noted in certain cancer types. However, whether the same phenomenon would occur in lung cancer is unclear. Here, we uncovered the molecular mechanism by which RSVL enhances the anticancer effect of GEM against lung cancer cells both in vitro and in vivo. We established human lung adenocarcinoma HCC827 xenografts in nude mice and treated them with GEM and RSVL to detect their synergistic effect in vivo. Tumor tissue sections from nude mice were subjected to hematoxylin and eosin staining for blood vessel morphological observation, and immunohistochemistry was conducted to detect CD31-positive staining blood vessels. We also established the HCC827-human umbilical vein endothelial cell (HUVEC) co-culture model to observe the tubule network formation. Human angiogenesis antibody array was used to screen the angiogenesis-related proteins in RSVL-treated HCC827. RSVL suppressed the expression of endoglin (ENG) and increased tumor microvessel growth and blood perfusion into tumor. Co-treatment of RSVL and GEM led to more tumor growth suppression than treatment of GEM alone. Mechanistically, using the HCC827-HUVEC co-culture model, we showed that RSVL-suppressed ENG expression was accompanied with augmented levels of phosphorylated extracellular signal-regulated kinase (ERK) 1/2 and increased tubule network formation, which may explain why RSVL promoted tumor microvessel growth in vivo. RSVL promoted tumor microvessel growth via ENG and ERK and enhanced the anticancer efficacy of GEM. Our results suggest that intake of RSVL may be beneficial during lung cancer chemotherapy.
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spelling pubmed-72259732020-05-18 Resveratrol Promotes Tumor Microvessel Growth via Endoglin and Extracellular Signal-Regulated Kinase Signaling Pathway and Enhances the Anticancer Efficacy of Gemcitabine against Lung Cancer Qin, San-Hai Lau, Andy T. Y. Liang, Zhan-Ling Tan, Heng Wee Ji, Yan-Chen Zhong, Qiu-Hua Zhao, Xiao-Yun Xu, Yan-Ming Cancers (Basel) Article The synergistic anticancer effect of gemcitabine (GEM) and resveratrol (RSVL) has been noted in certain cancer types. However, whether the same phenomenon would occur in lung cancer is unclear. Here, we uncovered the molecular mechanism by which RSVL enhances the anticancer effect of GEM against lung cancer cells both in vitro and in vivo. We established human lung adenocarcinoma HCC827 xenografts in nude mice and treated them with GEM and RSVL to detect their synergistic effect in vivo. Tumor tissue sections from nude mice were subjected to hematoxylin and eosin staining for blood vessel morphological observation, and immunohistochemistry was conducted to detect CD31-positive staining blood vessels. We also established the HCC827-human umbilical vein endothelial cell (HUVEC) co-culture model to observe the tubule network formation. Human angiogenesis antibody array was used to screen the angiogenesis-related proteins in RSVL-treated HCC827. RSVL suppressed the expression of endoglin (ENG) and increased tumor microvessel growth and blood perfusion into tumor. Co-treatment of RSVL and GEM led to more tumor growth suppression than treatment of GEM alone. Mechanistically, using the HCC827-HUVEC co-culture model, we showed that RSVL-suppressed ENG expression was accompanied with augmented levels of phosphorylated extracellular signal-regulated kinase (ERK) 1/2 and increased tubule network formation, which may explain why RSVL promoted tumor microvessel growth in vivo. RSVL promoted tumor microvessel growth via ENG and ERK and enhanced the anticancer efficacy of GEM. Our results suggest that intake of RSVL may be beneficial during lung cancer chemotherapy. MDPI 2020-04-15 /pmc/articles/PMC7225973/ /pubmed/32326402 http://dx.doi.org/10.3390/cancers12040974 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Qin, San-Hai
Lau, Andy T. Y.
Liang, Zhan-Ling
Tan, Heng Wee
Ji, Yan-Chen
Zhong, Qiu-Hua
Zhao, Xiao-Yun
Xu, Yan-Ming
Resveratrol Promotes Tumor Microvessel Growth via Endoglin and Extracellular Signal-Regulated Kinase Signaling Pathway and Enhances the Anticancer Efficacy of Gemcitabine against Lung Cancer
title Resveratrol Promotes Tumor Microvessel Growth via Endoglin and Extracellular Signal-Regulated Kinase Signaling Pathway and Enhances the Anticancer Efficacy of Gemcitabine against Lung Cancer
title_full Resveratrol Promotes Tumor Microvessel Growth via Endoglin and Extracellular Signal-Regulated Kinase Signaling Pathway and Enhances the Anticancer Efficacy of Gemcitabine against Lung Cancer
title_fullStr Resveratrol Promotes Tumor Microvessel Growth via Endoglin and Extracellular Signal-Regulated Kinase Signaling Pathway and Enhances the Anticancer Efficacy of Gemcitabine against Lung Cancer
title_full_unstemmed Resveratrol Promotes Tumor Microvessel Growth via Endoglin and Extracellular Signal-Regulated Kinase Signaling Pathway and Enhances the Anticancer Efficacy of Gemcitabine against Lung Cancer
title_short Resveratrol Promotes Tumor Microvessel Growth via Endoglin and Extracellular Signal-Regulated Kinase Signaling Pathway and Enhances the Anticancer Efficacy of Gemcitabine against Lung Cancer
title_sort resveratrol promotes tumor microvessel growth via endoglin and extracellular signal-regulated kinase signaling pathway and enhances the anticancer efficacy of gemcitabine against lung cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225973/
https://www.ncbi.nlm.nih.gov/pubmed/32326402
http://dx.doi.org/10.3390/cancers12040974
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