Nonsteroidal anti-inflammatory drugs may prevent colon cancer through suppression of hepatocyte growth factor expression

Autor: Shinichi Ota, Fukashi Matsuzaki, Yasuhiro Tanaka, Hiromi Bamba, Akira Kato
Rok vydání: 1999
Předmět:
Cholera Toxin
medicine.medical_specialty
Cell Survival
Colon
medicine.medical_treatment
Indomethacin
Gene Expression
Prostaglandin
Dinoprostone
chemistry.chemical_compound
Internal medicine
Cyclic AMP
medicine
Humans
Receptors
Prostaglandin E
Growth factor receptor inhibitor
RNA
Messenger
Alprostadil
Prostaglandin E2
Cells
Cultured
Pharmacology
Mucous Membrane
biology
Hepatocyte Growth Factor
Anti-Inflammatory Agents
Non-Steroidal
Membrane Proteins
Fibroblasts
Receptors
Prostaglandin E
EP2 Subtype
Isoenzymes
Endocrinology
Mechanism of action
chemistry
Cyclooxygenase 2
Prostaglandin-Endoperoxide Synthases
Colonic Neoplasms
Cyclooxygenase 1
Prostaglandins
Cancer research
biology.protein
Hepatocyte growth factor production
Hepatocyte growth factor
Cyclooxygenase
medicine.symptom
Receptors
Prostaglandin E
EP4 Subtype
Interleukin-1
Prostaglandin E
medicine.drug
Zdroj: European Journal of Pharmacology. 367:131-138
ISSN: 0014-2999
Popis: Nonsteroidal anti-inflammatory drugs which inhibit cyclooxygenase have been reported to suppress colon carcinogenesis. However the mechanism has not yet been elucidated. Growth factors such as hepatocyte growth factor, which are produced by fibroblasts, have been shown to be important in carcinogenesis and the progression of various human cancers. In the present study, we tested the hypothesis that nonsteroidal anti-inflammatory drugs inhibit hepatocyte growth factor expression through an endogenous prostaglandin-mediated pathway in cultured human colonic fibroblasts. Human colonic fibroblasts were obtained from a resected colon and cultured. Hepatocyte growth factor and prostaglandin E 2 were measured by enzyme-linked immunosorbent assay. Induction of cyclooxygenase-1 and cyclooxygenase-2 protein was estimated by immunoblotting. Prostaglandins increased hepatocyte growth factor production significantly in a dose- and time-dependent manner. Cholera toxin and 8-bromo cAMP also stimulated hepatocyte growth factor production. Further, prostaglandin E 1 significantly increased cellular cAMP. The prostaglandin EP 2 and EP 4 receptors were detected by reverse transcription-polymerase chain reaction. Interleukin-1β dramatically increased prostaglandin E 2 production and significantly stimulated hepatocyte growth factor synthesis. Interleukin-1β induced cyclooxygenase-2 but not cyclooxygenase-1 protein. Indomethacin significantly reduced interleukin-1β-induced prostaglandin E 2 release and hepatocyte growth factor production. These results suggest that prostaglandin is a factor for the production of hepatocyte growth factor by human colonic fibroblasts. Nonsteroidal anti-inflammatory drugs may suppress colon carcinogenesis, in part, through the suppression of hepatocyte growth factor expression by inhibiting endogenous prostaglandin production.
Databáze: OpenAIRE
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