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Volume 12
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10.3390/cancers12040974
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Article

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

by
San-Hai Qin
†,
Andy T. Y. Lau
†,
Zhan-Ling Liang
,
Heng Wee Tan
,
Yan-Chen Ji
,
Qiu-Hua Zhong
,
Xiao-Yun Zhao
and
Yan-Ming Xu
*
Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041, China
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cancers 2020, 12(4), 974; https://doi.org/10.3390/cancers12040974
Submission received: 14 March 2020 / Revised: 10 April 2020 / Accepted: 13 April 2020 / Published: 15 April 2020
(This article belongs to the Special Issue Angiogenesis in Cancers)
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Abstract

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.
Keywords: resveratrol; gemcitabine; endoglin; ERKs; microvessel growth; lung cancer resveratrol; gemcitabine; endoglin; ERKs; microvessel growth; lung cancer

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MDPI and ACS Style

Qin, S.-H.; Lau, A.T.Y.; Liang, Z.-L.; Tan, H.W.; Ji, Y.-C.; Zhong, Q.-H.; Zhao, X.-Y.; Xu, Y.-M. Resveratrol Promotes Tumor Microvessel Growth via Endoglin and Extracellular Signal-Regulated Kinase Signaling Pathway and Enhances the Anticancer Efficacy of Gemcitabine against Lung Cancer. Cancers 2020, 12, 974. https://doi.org/10.3390/cancers12040974

AMA Style

Qin S-H, Lau ATY, Liang Z-L, Tan HW, Ji Y-C, Zhong Q-H, Zhao X-Y, Xu Y-M. Resveratrol Promotes Tumor Microvessel Growth via Endoglin and Extracellular Signal-Regulated Kinase Signaling Pathway and Enhances the Anticancer Efficacy of Gemcitabine against Lung Cancer. Cancers. 2020; 12(4):974. https://doi.org/10.3390/cancers12040974

Chicago/Turabian Style

Qin, San-Hai, Andy T. Y. Lau, Zhan-Ling Liang, Heng Wee Tan, Yan-Chen Ji, Qiu-Hua Zhong, Xiao-Yun Zhao, and Yan-Ming Xu. 2020. "Resveratrol Promotes Tumor Microvessel Growth via Endoglin and Extracellular Signal-Regulated Kinase Signaling Pathway and Enhances the Anticancer Efficacy of Gemcitabine against Lung Cancer" Cancers 12, no. 4: 974. https://doi.org/10.3390/cancers12040974

APA Style

Qin, S.-H., Lau, A. T. Y., Liang, Z.-L., Tan, H. W., Ji, Y.-C., Zhong, Q.-H., Zhao, X.-Y., & Xu, Y.-M. (2020). Resveratrol Promotes Tumor Microvessel Growth via Endoglin and Extracellular Signal-Regulated Kinase Signaling Pathway and Enhances the Anticancer Efficacy of Gemcitabine against Lung Cancer. Cancers, 12(4), 974. https://doi.org/10.3390/cancers12040974

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