Prevention of Azoxymethane-Induced Colon Cancer by Combination of Low Doses of Atorvastatin, Aspirin, and Celecoxib in F 344 Rats
| Autor: | Xi Zheng, Tin Oo Khor, Levy Kopelovich, Chung Xiou Wang, Vernon E. Steele, Chinthalapally V. Rao, Bandaru S. Reddy, Ah-Ng Tony Kong |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Cancer Research medicine.medical_specialty Colorectal cancer Atorvastatin Azoxymethane Apoptosis Cell Growth Processes chemistry.chemical_compound Internal medicine medicine Animals Anticarcinogenic Agents Pyrroles Sulfonamides Aspirin Dose-Response Relationship Drug biology business.industry medicine.disease Hydroxymethylglutaryl-CoA reductase Rats Inbred F344 Rats Endocrinology Oncology chemistry Celecoxib Heptanoic Acids Colonic Neoplasms Toxicity HMG-CoA reductase Carcinogens biology.protein Pyrazoles business medicine.drug |
| Zdroj: | Cancer Research. 66:4542-4546 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-05-4428 |
| Popis: | Preclinical and clinical studies have provided evidence that aspirin, celecoxib, (cyclooxygenase-2 inhibitor), and statins (3-hydroxy-3-methylglutaryl CoA reductase inhibitors) inhibit colon carcinogenesis. Chronic use of high doses of these agents may induce side effects in ostensibly normal individuals. Combining low doses of agents may be an effective way to increase their efficacy and minimize toxicity. We assessed the efficacy of atorvastatin (lipitor), celecoxib, and aspirin, given individually at high dose levels and in combination at lower doses against azoxymethane-induced colon carcinogenesis, in male F 344 rats. One day after the last azoxymethane treatment (15 mg/kg body weight, s.c., once weekly for 2 weeks), groups of male F 344 rats were fed the AIN-76A diet or AIN-76A diet containing 150 ppm atorvastatin, 600 ppm celecoxib, and 400 ppm aspirin, 100 ppm atorvastatin + 300 ppm celecoxib, and 100 ppm atorvastatin + 200 ppm aspirin. Rats were killed 42 weeks later, and colon tumors were processed histopathologically and analyzed for cell proliferation and apoptosis immunohistochemically. Administration of these agents individually and in combination significantly suppressed the incidence and multiplicity of colon adenocarcinomas. Low doses of these agents in combination inhibited colon carcinogenesis more effectively than when they were given individually at higher doses. Inhibition of colon carcinogenesis by these agents is associated with the inhibition of cell proliferation and increase in apoptosis in colon tumors. These observations are of clinical significance because this can pave the way for the use of combinations of these agents in small doses against colon cancer. (Cancer Res 2006; 66(8): 4542-6) |
| Databáze: | OpenAIRE |
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