Overexpression of both VEGF-A and VEGF-C in gastric cancer correlates with prognosis, and silencing of both is effective to inhibit cancer growth.

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.