Cyclooxygenase-2 upregulates vascular endothelial growth factor expression and angiogenesis in human gastric carcinoma

  • Authors:
    • Wai K. Leung
    • Ka F. To
    • Minnie Y.Y. Go
    • Ka-Kui Chan
    • Francis K.L. Chan
    • Enders K.W. Ng
    • S. C.Sydney Chung
    • Joseph J.Y. Sung
  • View Affiliations

  • Published online on: November 1, 2003     https://doi.org/10.3892/ijo.23.5.1317
  • Pages: 1317-1322
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Abstract

Although gastric cancer with cyclooxygenase (COX)-2 overexpression is associated with poor prognosis, the mechanistic pathway remains unknown. We examined the associations between expressions of COX-2 and vascular endothelial growth factor (VEGF) in both gastric cancer cells and in human gastric cancer. The gastric cell line, Kato III, was transiently transfected with cox-2 expressing vector. The levels of COX-2, prostaglandin (PG) E2 and VEGF expression were measured post-transfection. Additionally, expressions of COX-2 and VEGF in human gastric cancer were determined by immunohistochemistry in archive gastrectomy specimens. Tumor angiogenesis was assessed by the microvessel density (MVD), which was determined by anti-CD34 immunostaining. Transient transfection of Kato III with cox-2 was associated with increased COX-2 expression, higher PGE2 production and upregulated VEGF expressions. Treatment with NS398, a specific COX-2 inhibitor, reduced VEGF expression in COX-2 expressing Kato III cells by 25%. Among the 67 gastric cancers examined, COX-2 overexpression was found in 45 (67%) cases whereas increased VEGF expression was detected in 46 (69%) cases. There was a significant association between COX-2 and VEGF expressions in gastric cancer (r=0.25, p=0.041). Additionally, tumor MVD was associated with both COX-2 (r=0.32, p=0.008) and VEGF (r=0.39, p=0.001) expressions. Our results showed that overexpression of COX-2 in both gastric cells and primary gastric cancer is associated with upregulation of VEGF and angiogenesis. Future studies should evaluate the potential anti-angiogenic effect of COX-2 inhibitors on human gastric cancer.

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November 2003
Volume 23 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Leung, W.K., To, K.F., Go, M.Y., Chan, K., Chan, F.K., Ng, E.K. ... Sung, J.J. (2003). Cyclooxygenase-2 upregulates vascular endothelial growth factor expression and angiogenesis in human gastric carcinoma. International Journal of Oncology, 23, 1317-1322. https://doi.org/10.3892/ijo.23.5.1317
MLA
Leung, W. K., To, K. F., Go, M. Y., Chan, K., Chan, F. K., Ng, E. K., Chung, S. C., Sung, J. J."Cyclooxygenase-2 upregulates vascular endothelial growth factor expression and angiogenesis in human gastric carcinoma". International Journal of Oncology 23.5 (2003): 1317-1322.
Chicago
Leung, W. K., To, K. F., Go, M. Y., Chan, K., Chan, F. K., Ng, E. K., Chung, S. C., Sung, J. J."Cyclooxygenase-2 upregulates vascular endothelial growth factor expression and angiogenesis in human gastric carcinoma". International Journal of Oncology 23, no. 5 (2003): 1317-1322. https://doi.org/10.3892/ijo.23.5.1317