title: Overexpression of both VEGF-A and VEGF-C in gastric cancer correlates with prognosis, and silencing of both is effective to inhibit cancer growth.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gastroenternology, Institute of Digestive Disease, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, PR China. wang455342@sina.com
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Wang
authors.forename: Ximei
authors.initials: X
authors.lastname: Chen
authors.forename: Jianping
authors.initials: J
authors.lastname: Fang
authors.forename: Changqing
authors.initials: C
authors.lastname: Yang
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D020868:Gene Silencing; D006801:Humans; D066298:In Vitro Techniques; D016086:Lentivirus / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D011379:Prognosis; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology* / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D042582:Vascular Endothelial Growth Factor C / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C
keywords: Vascular endothelial growth factor-A; gastric cancer; prognosis; tumor growth; vascular endothelial growth factor-C