A murine vascular endothelial growth factor antibody inhibits in vivo growth of human Caki-I renal adenocarcinoma

Anticancer Res. 2003 Mar-Apr;23(2B):1625-30.

Abstract

A number of studies have provided indirect evidence that angiogenesis is involved in tumour growth and metastasis formation of renal cell carcinoma (RCC). Nude mice bearing xenografts of human Caki-I RCC were treated i.p. for 3 weeks with a murine monoclonal antibody against vascular endothelial growth factor, VEGF (VEGF-ab). Tumour growth and mRNA expression of human and murine VEGF and murine VE-Cadherin in the tumours were measured. After 3 weeks of therapy, the tumour volume in the control nude mice was 548 +/- 98 mm3 compared to the tumours in the nude mice treated with VEGF-ab (122 +/- 24 mm3, p < 0.01). Treatment with VEGF-ab significantly reduced mRNA expression of murine VEGF-120 and murine VE-Cadherin (p < 0.05 and p < 0.01, respectively). The mRNA expression of human VEGF (hVEGF165, hVEGF189) and murine VEGF (mVEGF164) was unchanged due to antibody treatment. The mean percentage of apoptotic cells in tumours harvested from antibody-treated animals was significantly lower than in tumours from the control-treated animals (p < 0.02). These findings demonstrate for the first time that VEGF-ab significantly inhibit the growth of Caki-1 RCC in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • Antigens, CD
  • Apoptosis / drug effects
  • Cadherins / biosynthesis
  • Cadherins / genetics
  • Carcinoma, Renal Cell / secondary
  • Carcinoma, Renal Cell / therapy*
  • Endothelial Growth Factors / antagonists & inhibitors
  • Endothelial Growth Factors / biosynthesis
  • Endothelial Growth Factors / genetics
  • Endothelial Growth Factors / immunology*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Immunotherapy*
  • Intercellular Signaling Peptides and Proteins / biosynthesis
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / immunology*
  • Kidney Neoplasms / pathology*
  • Lymphokines / antagonists & inhibitors
  • Lymphokines / biosynthesis
  • Lymphokines / genetics
  • Lymphokines / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / immunology*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • RNA, Neoplasm / biosynthesis
  • RNA, Neoplasm / genetics
  • Skin Neoplasms / secondary
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Cadherins
  • Endothelial Growth Factors
  • Intercellular Signaling Peptides and Proteins
  • Lymphokines
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • cadherin 5