Targeted inhibition of COX-2 expression by RNA interference suppresses tumor growth and potentiates chemosensitivity to cisplatin in human gastric cancer cells

  • Authors:
    • Michael W.Y. Chan
    • Christine Y.P. Wong
    • Alfred S.L. Cheng
    • Victor Y.W. Chan
    • Ka K. Chan
    • Ka F. To
    • Francis K.L. Chan
    • Joseph J.Y. Sung
    • Wai K. Leung
  • View Affiliations

  • Published online on: December 1, 2007     https://doi.org/10.3892/or.18.6.1557
  • Pages: 1557-1562
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Abstract

Although selective cyclooxygenase-2 (COX-2) inhibitors suppress cell proliferation in gastric cancer, it remains debatable whether their effect is mediated through COX-2 dependent or independent pathways. We investigated the effects of the targeted inhibition of COX-2 expression by small interfering RNA (siRNA) in human gastric cancer cells and compared it to the effects of treatment with a specific COX-2 inhibitor. COX-2 mRNA and proteins were significantly reduced by up to 80% on day 2 after COX-2 siRNA transfection to the gastric cancer cell line MKN45. Concentrations of prostaglandins E2 (PGE2) in the condition medium were also reduced to 30% after siRNA transfection. Transfection of COX-2 siRNA exhibited a more potent anti-proliferative effect on MKN45 cells than treatment with high-dose (100 µM) NS398. COX-2 siRNA also significantly reduced tumor growth in nude mice. While COX-2 siRNA transfection alone had no obvious pro-apoptotic effects, unlike low-dose (10 µM) NS398 it enhanced the apoptotic reaction of MKN45 cells to cisplatin therapy. In conclusion, our results demonstrate for the first time that COX-2 siRNA inhibits cell growth and enhances the chemosensitivity of gastric cancer cells. RNA interference may be a promising alternative to specific COX-2 inhibitors in the prevention and treatment of gastric cancer.

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December 2007
Volume 18 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Chan MW, Wong CY, Cheng AS, Chan VY, Chan KK, To KF, Chan FK, Sung JJ and Leung WK: Targeted inhibition of COX-2 expression by RNA interference suppresses tumor growth and potentiates chemosensitivity to cisplatin in human gastric cancer cells. Oncol Rep 18: 1557-1562, 2007.
APA
Chan, M.W., Wong, C.Y., Cheng, A.S., Chan, V.Y., Chan, K.K., To, K.F. ... Leung, W.K. (2007). Targeted inhibition of COX-2 expression by RNA interference suppresses tumor growth and potentiates chemosensitivity to cisplatin in human gastric cancer cells. Oncology Reports, 18, 1557-1562. https://doi.org/10.3892/or.18.6.1557
MLA
Chan, M. W., Wong, C. Y., Cheng, A. S., Chan, V. Y., Chan, K. K., To, K. F., Chan, F. K., Sung, J. J., Leung, W. K."Targeted inhibition of COX-2 expression by RNA interference suppresses tumor growth and potentiates chemosensitivity to cisplatin in human gastric cancer cells". Oncology Reports 18.6 (2007): 1557-1562.
Chicago
Chan, M. W., Wong, C. Y., Cheng, A. S., Chan, V. Y., Chan, K. K., To, K. F., Chan, F. K., Sung, J. J., Leung, W. K."Targeted inhibition of COX-2 expression by RNA interference suppresses tumor growth and potentiates chemosensitivity to cisplatin in human gastric cancer cells". Oncology Reports 18, no. 6 (2007): 1557-1562. https://doi.org/10.3892/or.18.6.1557