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Combined silencing of VEGF-A and angiopoietin-2, a more effective way to inhibit the Ishikawa endometrial cancer cell line

Authors Xu X, Yan Y, Xun Q, Shi J, Kong X, Wu J, Zhou H

Received 9 November 2018

Accepted for publication 20 January 2019

Published 14 February 2019 Volume 2019:12 Pages 1215—1223

DOI https://doi.org/10.2147/OTT.S194064

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Dr XuYu Yang


Xiaofeng Xu,1,* Yuhua Yan,1,2,* Qingying Xun,3 Jiayu Shi,1,4 Xiangyi Kong,1 Jun Wu,1 Huaijun Zhou1

1Department of Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu 210008, China; 2Department of Gynecology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, China; 3Department of Physiology, Medical College, Southeast University, Nanjing, Jiangsu 210009, China; 4Department of Obstetrics and Gynecology, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, Henan 450008, China

*These authors contributed equally to this work

Background: Angiogenesis is critical for the growth and metastasis of solid tumors and is, therefore, an important therapeutic target. Despite the great research advances in tumor therapies targeting vascular endothelial growth factor (VEGF), drug resistance frequently occurs, and further strategies targeting the tumor vasculature are of primary concern.
Purpose: The present study aimed to determine whether a combination of small interfering RNAs (siRNAs) targeting VEGF-A and angiopoietin-2 (Ang-2) inhibited the biologic mechanisms of endometrial cancer more effectively compared to either one alone, in vitro and in vivo.
Methods: VEGF-A and Ang-2 were silenced by siRNA in Ishikawa endometrial cancer cells. Cell growth, apoptosis, metastasis, and tumor angiogenesis were measured in vitro and in vivo.
Results: There was no difference observed in cell apoptosis rate; however, combined silencing of VEGF-A and Ang-2 resulted in a stronger inhibition of cell proliferation and invasion (P<0.05). Similarly, a greater reduction of tumor size and angiogenesis was seen with the concurrent administration of siRNAs targeting VEGF-A and Ang-2 in nude mice (P<0.05).
Conclusion: Our data indicated that simultaneous blockade of VEGF-A and Ang-2 may serve as a novel and effective therapeutic strategy in endometrial cancer.

Keywords: drug resistance, siRNA, Ang-2, angiogenesis



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