Interleukin-1 receptor antagonist inhibits the expression of vascular endothelial growth factor in colorectal carcinoma

Oncology. 2005;68(2-3):138-45. doi: 10.1159/000086768. Epub 2005 Jul 4.


Objective: Interleukin (IL)-1 is known to act as a tumor growth factor by inducing angiogenic factors. We examined the significance of IL-1beta and IL-1 receptor antagonist (RA) for inducing the expression of vascular endothelial growth factor (VEGF) in colorectal cancers.

Methods: We investigated the expression of VEGF induced by IL-1beta in five colon cancer cell lines and the possible involvement of IL-1 RA. We also measured the tissue concentrations of IL-1beta, IL-1 RA and VEGF by ELISA in 65 colorectal cancer patients.

Results: IL-1beta induced VEGF secretion with a 19-fold increase in Caco-2 cells. A significant increase in VEGF secretion was also observed in SW480 and WiDr cells. IL-1 RA inhibited IL-1beta-induced VEGF secretion by 87%. Our data from the clinically obtained specimens showed that the IL-1 RA/IL-1beta ratio is significantly lower in cancer tissue. Regarding the clinicopathological parameters, the IL-1 RA/IL-1beta ratio was significantly lower in patients with vessel involvement than in those without involvement, and IL-1 RA/IL-1beta ratio was negatively correlated with the VEGF protein level in colorectal tumors.

Conclusions: Our data suggest that IL-1beta induces VEGF expression and IL-1 RA acts as the competitive inhibitor, and that the IL-1 RA/IL-1beta ratio is significant for VEGF expression in the microenvironment of colorectal cancer tissue. We conclude that IL-1beta induces VEGF secretion in a certain population of colorectal cancer patients, and that IL-1 RA is the potential therapeutic agent for antiangiogenic therapy in colorectal cancer patients.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / pharmacology*
  • Carcinoma / drug therapy*
  • Carcinoma / metabolism
  • Cell Line, Tumor
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Interleukin-1 / antagonists & inhibitors
  • Interleukin-1 / metabolism
  • Male
  • Middle Aged
  • RNA, Messenger / metabolism
  • Receptors, Interleukin-1 / antagonists & inhibitors*
  • Receptors, Interleukin-1 / metabolism
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / biosynthesis
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism*


  • Antineoplastic Agents
  • Interleukin-1
  • RNA, Messenger
  • Receptors, Interleukin-1
  • Vascular Endothelial Growth Factor A