Combined effects of cyclooxygenase-1 and cyclooxygenase-2 selective inhibitors on intestinal tumorigenesis in adenomatous polyposis coli gene knockout mice
| Autor: | Tomohiro Kitamura, Keiji Wakabayashi, Masaki Itoh, Mamoru Matsuura, Tetsuo Noda |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Cancer Research
medicine.medical_specialty Genes APC Ratón Adenomatous polyposis coli Indomethacin Intestinal polyp Mice Mofezolac Internal medicine Antineoplastic Combined Chemotherapy Protocols Intestinal Neoplasms medicine Animals Cyclooxygenase Inhibitors Anticarcinogen Mice Knockout Sulfonamides biology Cyclooxygenase 2 Inhibitors Chemistry Intestinal Polyps Membrane Proteins Isoxazoles Neoplasms Experimental Isoenzymes Endocrinology Oncology Enzyme inhibitor Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases biology.protein Cyclooxygenase 1 Cyclooxygenase medicine.drug Nimesulide |
| Zdroj: | International journal of cancer. 109(4) |
| ISSN: | 0020-7136 |
| Popis: | As with cyclooxygenase (COX)-2, genetic disruption of COX-1 gene or pharmacologic inhibition of its activity has been shown to decrease the number of intestinal polyps in Apc gene-deficient mice. The present study was designed to investigate the combined effects of COX-1 and COX-2 selective inhibitors on spontaneous polyp formation in APC1309 female mice. The animals were treated with 300 or 600 ppm mofezolac (a COX-1 selective inhibitor) alone, 200 or 400 ppm nimesulide (a COX-2 selective inhibitor) alone, 300 ppm mofezolac plus 200 ppm nimesulide, 600 ppm mofezolac plus 400 ppm nimesulide, or 10 ppm indomethacin (a dual-COX inhibitor) in the diet from 7 weeks of age for 4 weeks. Percentage inhibition of polyp area in the intestine was 17% with 600 ppm mofezolac alone and 25% with 400 ppm nimesulide alone, their sum of 42% being almost equal to the 37% observed for the combination treatment. Administration of 300 ppm mofezolac plus 200 ppm nimesulide also significantly decreased polyp area in the intestine by 30%. Moreover, the numbers of polyps more than 2.5 mm in diameter were markedly decreased by combined treatment of both COX inhibitors. With 10 ppm indomethacin, the dual inhibitor, polyp area was also clearly reduced by 46%. Our results indicate that COX-1 and COX-2 may to some extent contribute to polyp formation independently and inhibitor combination treatment thus has particular potential for chemoprevention of colon carcinogenesis. © 2004 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text