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Parthenolide Inhibits Angiogenesis in Esophageal Squamous Cell Carcinoma Through Suppression of VEGF

Authors Tian B, Xiao Y, Ma J, Ou W, Wang H, Wu J, Tang J, Zhang B, Liao X, Yang D, Wu Z, Li X, Zhou Y, Su M, Wang W

Received 31 March 2020

Accepted for publication 2 July 2020

Published 29 July 2020 Volume 2020:13 Pages 7447—7458

DOI https://doi.org/10.2147/OTT.S256291

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Federico Perche


Bo Tian,1,2 Yuhang Xiao,3 Junliang Ma,1,2 Wei Ou,4 Hui Wang,2 Jie Wu,1 Jinming Tang,1 Baihua Zhang,1 Xiaojuan Liao,5 Desong Yang,1 Zhining Wu,1 Xu Li,1 Yong Zhou,1 Min Su,1,2 Wenxiang Wang1,2

1Department of the 2nd Thoracic Surgery, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, People’s Republic of China; 2Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, People’s Republic of China; 3Department of Pharmacy, Xiangya Hospital of Xiangya School of Medicine, Central South University, Changsha, People’s Republic of China; 4Department of Pharmacy, The First People’s Hospital of Yue Yang, Yue Yang, People’s Republic of China; 5Department of Pharmacy, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, People’s Republic of China

Correspondence: Wenxiang Wang; Min Su Tel/ Fax +86-731-89762110
Email hnchw11@163.com; sumin27@126.com

Background: Parthenolide (PT), the effective active ingredient of the medicinal plant, feverfew (Tanacetum parthenium), has been used as an anti-inflammatory drug due to its involvement in the inhibition of the NF-кB pathway. Moreover, recent studies have demonstrated the anti-tumor effect of PT in several cancers. However, the effect of PT on esophageal carcinoma remains unclear to date. In this study, we examined the inhibitory effects of PT and its underlying mechanism of action in human esophageal squamous cell carcinoma (ESCC) cells – Eca109 and KYSE-510.
Methods: The proliferation ability of Eca109 and KYSE-510 treated with PT was detected using the Cell Counting Kit-8 and colony forming assay. The Transwell assay and the wound healing assay were used to analyze the cell invasion and migration ability, respectively. The tube formation assay was used to investigate the effect of PT on tube formation of endothelial cells. The expression level of NF-кB, AP-1 and VEGF was analyzed by Western blot.
Results: We demonstrated that PT attenuates the proliferation and migration ability of ESCC cells in vitro and also inhibits tumor growth in the mouse xenograft model. In addition, PT exhibited anti-angiogenesis activity by weakening the proliferation, invasion and tube formation of endothelial cells in vitro and reduced microvessel density in the xenograft tumors. Further studies revealed that PT reduced the expression level of NF-кB, AP-1 and VEGF in ESCC cells.
Conclusion: Collectively, the results of our study demonstrated that PT exerts anti-tumor and anti-angiogenesis effects possibly by inhibiting the NF-кB/AP-1/VEGF signaling pathway on esophageal carcinoma and might serve as a promising therapeutic agent for ESCC.

Keywords: parthenolide, esophageal squamous cell carcinoma, NF-кB, VEGF, AP-1

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