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Resveratrol Suppresses Tumor Progression via Inhibiting STAT3/HIF-1α/VEGF Pathway in an Orthotopic Rat Model of Non-Small-Cell Lung Cancer (NSCLC)

Authors Wang H, Jia R, Lv T, Wang M, He S, Zhang X

Received 20 April 2020

Accepted for publication 5 June 2020

Published 21 July 2020 Volume 2020:13 Pages 7057—7063

DOI https://doi.org/10.2147/OTT.S259016

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Nicola Silvestris


Huixia Wang,1 Ruzhen Jia,1 Tianle Lv,1 Mei Wang,1 Shiwei He,1 Xia Zhang2

1Respiratory Department, The People’s Hospital of Baoji City, Baoji, Shaanxi 721000, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Central Hospital of Hanzhong City, Hanzhong, Shaanxi 723000, People’s Republic of China

Correspondence: Xia Zhang
Department of Pulmonary and Critical Care Medicine, Central Hospital of Hanzhong City, No. 277, Kangfu Road, Hanzhong, Shaanxi 723000, People’s Republic of China
Tel/ Fax +86 916-2680145
Email zhangxia01056@163.com

Background: The STAT3/HIF-1α/VEGF pathway is associated with the development and progress of various tumors including NSCLC. The aim of the present study was to investigate whether resveratrol (RES) could suppress NSCLC progression via inhibiting the expressions of STAT3, HIF-1α, and VEGF in a nude rat model.
Methods: Twenty-four nude rats were randomly divided into control, NSCLC, and NSCLC+RES groups. An orthotopic rat model of NSCLC was established. The animals in the NSCLC+RES group received the same operation as the NSCLC group and were intragastrically administered RES at 250 mg/kg/day for 12 weeks. Lung tissue samples were harvested for gross tumor burden measurement, histological examinations, RT-PCR, and Western blot assays.
Results: In the NSCLC+RES group, significant decreases in lung weight index, lung tumor burden, STAT3/HIF-1α/VEGF mRNA, and protein levels were observed when compared with the NSCLC group (all P< 0.05). The structural integrity of the lung was less affected and the apoptotic index was significantly higher in the NSCLC+RES group, when compared to the NSCLC group (P< 0.05).
Conclusion: RES suppresses NSCLC partly through inhibiting the expressions of STAT3, HIF-1α, and VEGF. The STAT3/HIF-1α/VEGF pathway might be a candidate drug target for developing new chemotherapy agents derived from RES for the treatment of NSCLC.

Keywords: resveratrol, non-small-cell lung cancer, STAT3, HIF-1α, VEGF, rat

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