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

Onco Targets Ther. 2016 Apr 12:9:2131-41. doi: 10.2147/OTT.S98002. eCollection 2016.

Abstract

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; AJCC staging; Fuhrman grading; HK-2; PI3K/AKT; cell biological behavior; siRNA; transfection.