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Downregulation of VEGFA inhibits proliferation, promotes apoptosis, and suppresses migration and invasion of renal clear cell carcinoma

Authors Zeng F, Zeng M, Huang L, Li Y, Gao B, Chen J, Xue R, Tang Z

Received 10 October 2015

Accepted for publication 21 December 2015

Published 12 April 2016 Volume 2016:9 Pages 2131—2141

DOI https://doi.org/10.2147/OTT.S98002

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Ram Prasad

Peer reviewer comments 3

Editor who approved publication: Professor Daniele Santini


Fan-Chang Zeng,1,2 Ming-Qiang Zeng,1 Liang Huang,1 Yong-Lin Li,1 Ben-Min Gao,1 Jun-Jie Chen,1 Rui-Zhi Xue,1 Zheng-Yan Tang1

1Department of Urology, Xiangya Hospital, Central South University, Changsha, 2Department of Urology, Hainan General Hospital, Haikou, People’s Republic of China

Objective: The aim of this study was to investigate the effects of vascular endothelial growth factor A (VEGFA) on cell proliferation, apoptosis, migration, and invasion in renal clear cell carcinoma (RCCC).
Methods: Between June 2012 and June 2015, RCCC tissues were obtained for the experimental group, and RCCC adjacent tumor-free kidney parenchyma tissues were obtained for the control group. VEGFA mRNA and protein expressions and phosphoinositide 3-kinase, serine/threonine-specific protein kinase (AKT), and phosphorylated-AKT protein expressions were detected. The chemically synthesized specific siRNA using RNA interference technology was used to inhibit VEGFA gene expression in human RCCC 786-O cells. The negative control (NC) group was transfected with NC sequence, and the blank group was transfected with no sequence. Flow cytometry, scratch test, and cell-penetrating experiment were used to detect cell proliferation, apoptosis, migration, and invasion of 786-O cells.
Results:
Positive expression of VEGFA protein was 60.62% in RCCC tissue and 18.34% in adjacent tissue with statistically significant difference (P<0.001). VEGFA protein and mRNA expressions were higher in RCCC tissue than those in adjacent tissue (both P<0.01). VEGF expression in RCCC tissue was associated with Fuhrman grading and American Joint Committee on Cancer staging (both P<0.05). After RCCC 786-O cells transfecting the VEGFA siRNA, the VEGFA mRNA and protein expressions and phosphoinositide 3-kinase and phosphorylated-AKT protein expressions were significantly decreased, cell proliferation was remarkably inhibited, cell apoptotic ratio was obviously increased, and migration distance and invasive cell number were markedly decreased compared to those in the NC group and the blank group (all P<0.05).
Conclusion: Inhibition of VEGFA inhibited proliferation, promoted apoptosis, and suppressed migration and invasion of RCCC 786-O cells. VEGF has a potential role in diagnosis and therapy of RCCC.

Keywords: 786-O, siRNA, transfection, cell biological behavior, PI3K/AKT, Fuhrman grading, AJCC staging, HK-2

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