Inhibition of growth and metastasis of ovarian carcinoma by administering a drug capable of interfering with vascular endothelial growth factor activity

Jpn J Cancer Res. 1996 Sep;87(9):963-71. doi: 10.1111/j.1349-7006.1996.tb02127.x.


The present study investigates the relationship between in vivo growth/metastasis of tumor cells and their capacity to produce the vascular endothelial growth factor (VEGF), as well as the regulation of tumor growth/metastasis using an angiogenesis-inhibitory drug. Two cloned tumor cell lines designated OV-LM and OV-HM were isolated from a murine ovarian carcinoma OV2944. OV-LM and OV-HM cells grew in cultures at comparable rates. However, when transplanted s.c. into syngeneic mice, OV-HM exhibited a faster growth rate and a much higher incidence of metastasis to lymph nodes and lung. Histologically, intense neovascularization was detected in sections of OV-HM but not of OV-LM tumor. OV-HM and OV-LM tumor cells obtained from in vitro cultures expressed high and low levels of VEGF mRNA, respectively. A difference in VEGF mRNA expression was much more clearly observed between RNAs prepared from fresh OV-HM and OV-LM tumor masses: RNA from OV-HM contained larger amounts of VEGF mRNA, whereas RNA from OV-LM exhibited only marginal levels of VEGF mRNA. An angiogenesis-inhibitory drug, FR118487 inhibited the VEGF-mediated in vitro growth of endothelial cells but did not affect the expression in vitro of VEGF mRNA by OV-HM tumor cells. Intraperitoneal injections of FR118487 into mice bearing OV-HM tumors resulted in: (i) a subsequent growth inhibition of primary tumors; (ii) a marked decrease in neovascularization inside tumor masses expressing comparable levels of VEGF mRNA to those detected in control OV-HM masses; and (iii) almost complete inhibition of metastasis to lymph nodes and lung. These results indicate that growth/metastasis of tumor cells correlates with their VEGF-producing capacity and that an angiogenesis inhibitor, FR118487, inhibits tumor growth and metastasis through mechanism(s) including the suppression of VEGF function in vivo.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Cell Division / drug effects
  • Cells, Cultured
  • Endothelial Growth Factors / metabolism*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Female
  • Humans
  • Lung Neoplasms / secondary
  • Lymphatic Metastasis
  • Lymphokines / metabolism*
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Nude
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / metabolism*
  • Ovarian Neoplasms / blood supply*
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / pathology
  • RNA, Messenger / metabolism
  • Spiro Compounds / pharmacology*
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Endothelial Growth Factors
  • FR 118487
  • Lymphokines
  • RNA, Messenger
  • Spiro Compounds
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors