Cyclooxygenase-2 knockdown by RNA interference in colon cancer

  • Authors:
    • George S. Charames
    • Bharati Bapat
  • View Affiliations

  • Published online on: February 1, 2006     https://doi.org/10.3892/ijo.28.2.543
  • Pages: 543-549
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Abstract

Overexpression of cyclooxygenase-2 (COX-2) is observed early in colon cancer. Treatments with COX-2-specific NSAIDs have been shown to reduce polyp size and polyp number in FAP patients with a predisposition to colorectal adenoma and cancer. However, the use of COX-2-specific NSAIDs in colon cancer patients has recently revealed increased cardiovascular risks. These harmful side effects may be the result of COX-dependent and/or COX-independent mechanisms. RNA interference (RNAi) is a method of post-transcriptional gene silencing intrinsic to cells. This study employed RNAi to specifically knockdown endogenous COX-2 expression in the HT-29 colon cancer cell line, and to observe the apoptotic response as well as 15-hydroxyprostaglandin dehydrogenase (15-PGDH) expression levels. Following treatment with a COX-2 siRNA, we demonstrated a significant knockdown at the protein level of 57% as compared to a non-silencing siRNA control. Protein results were corroborated by concurrent decrease in COX-2 mRNA levels following the same treatment regimen. Despite previous studies using NSAID treatment to implicate COX-2 involvement in apoptosis, we did not observe any alteration in Bcl-2 expression and Caspase-3 activation following COX-2 knockdown in these cells. 15-PGDH, a physiological antagonist of COX-2 in its catabolism of PGE2, showed a modest but significant induction in response to COX-2 knockdown. The precise role of COX-2 in apoptosis and PGE2 regulation remains unclear; however, having shown that down-regulation of endogenous levels of COX-2 can be achieved in colon cancer by RNAi, this strategy should prove to be a valuable tool in revealing the specific function of COX-2 in tumourigenesis.

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February 2006
Volume 28 Issue 2

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

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Spandidos Publications style
Charames GS and Bapat B: Cyclooxygenase-2 knockdown by RNA interference in colon cancer. Int J Oncol 28: 543-549, 2006.
APA
Charames, G.S., & Bapat, B. (2006). Cyclooxygenase-2 knockdown by RNA interference in colon cancer. International Journal of Oncology, 28, 543-549. https://doi.org/10.3892/ijo.28.2.543
MLA
Charames, G. S., Bapat, B."Cyclooxygenase-2 knockdown by RNA interference in colon cancer". International Journal of Oncology 28.2 (2006): 543-549.
Chicago
Charames, G. S., Bapat, B."Cyclooxygenase-2 knockdown by RNA interference in colon cancer". International Journal of Oncology 28, no. 2 (2006): 543-549. https://doi.org/10.3892/ijo.28.2.543