Autocrine vascular endothelial growth factor/vascular endothelial growth factor receptor-2 growth pathway represents a cyclooxygenase-2-independent target for the cyclooxygenase-2 inhibitor NS-398 in colon cancer cells

Jin Kim Seok, Jae Hong Seo, Jung Lee Yoo, Hye Yoon Ji, Chul Won Choi, Byung Soo Kim, Sang Won Shin, Yeul Hong Kim, Jun Suk Kim

Research output: Contribution to journalArticle

19 Citations (Scopus)


Objectives: Coexpression of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 (VEGFR-2) has been reported in tumor cells, suggesting the presence of an autocrine VEGF/VEGFR-2 growth pathway in solid tumors. Thus, we hypothesize that the presence of this autocrine pathway in colon cancer cells may be a COX-2-independent target of COX-2 inhibitors and a mechanism behind the antitumor effects of these agents. Methods: COX-2-positive (Caco2, HT-29) and COX-2-negative colon cancer cells (DLD-1, Hct-15) were used. Expression of VEGFR-2 was evaluated by Western blot and reverse transcriptase-polymerase chain reaction and VEGF production was measured from culture supernatant by enzyme-linked immunosorbent assay. Growth inhibition and the expression of VEGF and VEGFR-2 were compared after treatment with the COX-2 inhibitor, NS-398 at doses ranging from 5 to 100 μM. Results: VEGF and VEGFR-2 were expressed in all four colon cancer cells and a blockade of VEGFR-2 with anti-VEGFR-2 antibody treatment induced growth inhibition of colon cancer cells, supporting the presence of autocrine VEGF/VEGFR-2 growth pathway. NS-398 suppressed the growth of colon cancer cells, independent of COX-2 expression. VEGFR-2 expression of tumor cells was reduced after NS-398 treatment at 100 μM, the concentration at which maximal growth inhibition was induced. The amount of VEGF in culture supernatant was increased by NS-398 at 100 μM, suggesting increased secretion of VEGF in compensation for reduced VEGFR-2 expression. Conclusion: The autocrine VEGF/VEGFR-2 growth pathway could be a COX-2-independent target of the COX-2 inhibitor, NS-398, in colon cancer cells.

Original languageEnglish
Pages (from-to)204-211
Number of pages8
Issue number2-3
Publication statusPublished - 2005 Jul 1



  • Colon cancer cell
  • Cyclooxygenase-2 inhibitor
  • Cyclooxygenase-2-independent target
  • VEGF/VEGFR-2 growth pathway, autocrine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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