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Modulation of Apoptosis and Bcl-2 Expression by Prostaglandin E2 in Human Colon Cancer Cells

Hongmiao Sheng, Jinyi Shao, Jason D. Morrow, R. Daniel Beauchamp and Raymond N. DuBois
Hongmiao Sheng
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Jinyi Shao
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Jason D. Morrow
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R. Daniel Beauchamp
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Raymond N. DuBois
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DOI:  Published January 1998
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Abstract

Previously, we have shown that forced expression of prostaglandin endoperoxide synthase-2 [also called cyclooxygenase (COX) 2] leads to inhibition of programmed cell death in intestinal epithelial cells. More recently, we have demonstrated that growth of human colonic cancer xenografts is inhibited by treatment with a highly selective COX-2 inhibitor in tumors that express COX-2 (HCA-7) but not in those that lack COX-2 expression (HCT-116). To explore the biochemical mechanisms involved in these effects, we have evaluated the role of COX-2-derived eicosanoid products on programmed cell death in human colon cancer cells. Here we report that PGE2 treatment of human colon cancer cells leads to increased clonogenicity of HCA-7, but not HCT-116 cells. Treatment with a highly selective COX-2 inhibitor (SC-58125) decreases colony formation in monolayer culture and this growth inhibition was reversed by treatment with PGE2. Additionally, PGE2 inhibits programmed cell death caused by SC-58125 and induces Bcl-2 expression, but did not affect Bcl-x or Bax expression in human colon cancer (HCA-7) cells. Therefore, decreased cell death caused by PGE2 would enhance the tumorigenic potential of intestinal epithelial cells. Thus, these results may help to explain a component of the mechanism by which COX inhibitors prevent colorectal cancer in humans.

Footnotes

  • ↵1 This study was supported by USPHS Grants DK-47297 (to R. N. D.), GM-53319 (to R. D. B.), CA-69457 (to R. D. B.), DK-48831 (to J. D. M.), GM-15431, and GM-42056 (to J. D. M.); National Institute of Environmental Health Sciences Grant 00267; and the Veterans Affairs Merit Grant (to R. N. D.).

  • ↵2 To whom requests for reprints should be addressed, at the Department of Medicine/GI, MCN C-2104, Vanderbilt University Medical Center, Nashville, TN 37232-2279. Phone: (615) 343-8989; Fax: (615) 343-6229; E-mail: duboism@ctrvax.vanderbilt.edu.

  • Received July 22, 1997.
  • Accepted November 11, 1997.
  • ©1998 American Association for Cancer Research.
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January 1998
Volume 58, Issue 2
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Modulation of Apoptosis and Bcl-2 Expression by Prostaglandin E2 in Human Colon Cancer Cells
Hongmiao Sheng, Jinyi Shao, Jason D. Morrow, R. Daniel Beauchamp and Raymond N. DuBois
Cancer Res January 15 1998 (58) (2) 362-366;

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Modulation of Apoptosis and Bcl-2 Expression by Prostaglandin E2 in Human Colon Cancer Cells
Hongmiao Sheng, Jinyi Shao, Jason D. Morrow, R. Daniel Beauchamp and Raymond N. DuBois
Cancer Res January 15 1998 (58) (2) 362-366;
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