Inhibition of human colon cancer cell growth by selective inhibition of cyclooxygenase-2
| Autor: | Hongmiao Sheng, P Isakson, Raymond N. DuBois, S C Kirkland, Jinyi Shao, Jason D. Morrow, Robert J. Coffey, R D Beauchamp |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
medicine.medical_specialty
Cell division Colorectal cancer Blotting Western Transplantation Heterologous Mice Nude Biology Mice chemistry.chemical_compound Internal medicine Tumor Cells Cultured medicine Animals Humans Cyclooxygenase Inhibitors Aspirin Cyclooxygenase 2 Inhibitors Cell growth Membrane Proteins General Medicine Blotting Northern medicine.disease Isoenzymes Transplantation Endocrinology chemistry Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases Cell culture Cyclooxygenase 1 Prostaglandins Cancer research biology.protein Pyrazoles RNA Arachidonic acid Cyclooxygenase Colorectal Neoplasms Cell Division Research Article medicine.drug |
| Zdroj: | Journal of Clinical Investigation. 99:2254-2259 |
| ISSN: | 0021-9738 |
| Popis: | A considerable amount of evidence collected from several different experimental systems indicates that cyclooxygenase-2 (COX-2) may play a role in colorectal tumorigenesis. Large epidemiologic studies have shown a 40-50% reduction in mortality from colorectal cancer in persons taking aspirin or other nonsteroidal antiinflammatory drugs on a regular basis. One property shared by all of these drugs is their ability to inhibit COX, a key enzyme in the conversion of arachidonic acid to prostaglandins. Two isoforms of COX have been characterized, COX-1 and COX-2. COX-2 is expressed at high levels in intestinal tumors in humans and rodents. In this study, we selected two transformed human colon cancer cell lines for studies on the role of COX-2 in intestinal tumorigenesis. We evaluated HCA-7 cells which express high levels of COX-2 protein constitutively and HCT-116 cells which lack COX-2 protein. Treatment of nude mice implanted with HCA-7 cells with a selective COX-2 inhibitor (SC-58125), reduced tumor formation by 85-90%. SC-58125 also inhibited colony formation of cultured HCA-7 cells. Conversely, SC-58125 had no effect on HCT-116 implants in nude mice or colony formation in culture. Here we provide evidence that there may be a direct link between inhibition of intestinal cancer growth and selective inhibition of the COX-2 pathway. |
| Databáze: | OpenAIRE |
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