IJCEP Copyright © 2007-All rights reserved.
Int J Clin Exp Pathol 2013;6(4):586-597

Original Article
Overexpression of both VEGF-A and VEGF-C in gastric cancer corre-lates with
prognosis, and silencing of both is effective to inhibit cancer growth

Xiaolei Wang, Ximei Chen, Jianping Fang, Changqing Yang

Department of Gastroenternology, Institute of Digestive Disease, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, PR
China; Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, PR China

Received January 9, 2013; Accepted February 26, 2013; Epub March 15, 2013; Published April 1, 2013

Abstract: Background: Vascular endothelial growth factor (VEGF)-A and VEGF-C are two important molecules involving in tumor development
and metastasis via angiogenesis and lymphangiogenesis. However, the combined effect of VEGF-A and VEGF-C on the growth of gastric
cancer (GC) is not clear. Methods: The correlations of VEGF-A and VEGF-C expressions with clinicopathologic parameters and prognosis were
evaluated in patients with GC. Furthermore, lentivirus-mediated RNA interfering (RNAi) targeting VEGF-A and/or VEGF-C was employed to
silence their expressions in SGC7901 GC cell line. Cell proliferation and apoptosis were measured in vitro. Suppressive effect lentivirus-
mediated VEGF-A and/or VEGF-C silencing on GC growth was evaluated in GC bearing mice. Results: The patients with high expression of
both VEGF-A and VEGF-C (A+C+) had larger tumor size, higher peritumoral lymphatic vessel density(P-LVD), microvessel density(MVD),
lymphatic vessel invasion (LVI), lymph node(LN) metastasis, and worse prognosis than those with low expression of both VEGF-A and VEGF-C
(P<0.05). Lentivirus-mediated RNAi significantly reduced the mRNA and protein expression of VEGF-A and VEGF-C in the SGC7901 cells. The
Lenti-miRNA-VEGF-A+VEGF-C significantly inhibited the cell proliferation and tumor growth, compared with Lenti-miRNA-VEGF-A or Lenti-
miRNA-VEGF-C (P<0.05). In addition, Lenti-miRNA- VEGF-A+VEGF-C markedly lowered the tumor size in vivo in comparison with Lenti-miRNA-
VEGF-A or Lenti-miRNA–VEGF-C (P<0.05). Conclusion: Expressions of both VEGF-A and VEGF-C predict worse prognosis of GC patients.
Combined silencing of VEGF-A and VEGF-C markedly suppresses cancer growth than silencing of VEGF-A or VEGF-C. Thus, to inhibit the
expressions of VEGF-A and VEGF-C may become a novel strategy for the treatment of GC. (IJCEP1301019).

Keywords: Vascular endothelial growth factor-A, vascular endothelial growth factor-C, tumor growth, prognosis, gastric cancer

Address correspondence to: Dr. Xiao-Lei Wang, Department of Gastroenterology, Institute of Digestive Disease, Tongji Hospital, Tongji Univer-
sity School of Medicine, Shanghai 200065, PR China. Phone: 13817267967; E-mail: wang455342@sina.com, wangxiaolei@tongji.edu.cn