Roxatidine- and Cimetidine-Induced Angiogenesis Inhibition Suppresses Growth of Colon Cancer Implants in Syngeneic Mice
| Autor: | Kazuki Izumi, Susumu Okabe, Kazuyoshi Tomita |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Male
Colorectal cancer Angiogenesis Angiogenesis Inhibitors Pharmacology Neovascularization Mice chemistry.chemical_compound Piperidines Cell Line Tumor Animals Medicine Gastrointestinal cancer Cimetidine Neovascularization Pathologic business.industry Cell growth lcsh:RM1-950 medicine.disease Xenograft Model Antitumor Assays Mice Inbred C57BL Vascular endothelial growth factor lcsh:Therapeutics. Pharmacology chemistry Colonic Neoplasms Molecular Medicine medicine.symptom business Histamine medicine.drug |
| Zdroj: | Journal of Pharmacological Sciences, Vol 93, Iss 3, Pp 321-330 (2003) |
| ISSN: | 1347-8648 1347-8613 |
| DOI: | 10.1254/jphs.93.321 |
| Popis: | Cimetidine is known to suppress the growth of several tumors, including gastrointestinal cancer, in humans and animals. Nonetheless, whether other histamine H2-receptor antagonists exert such tumor suppressive effects remains unclear. The effect of roxatidine acetate hydrochloride (roxatidine), an H2-receptor antagonist, on the growth of colon cancer implanted in mice was examined and compared with that of cimetidine. Drugs were orally delivered for 26 – 29 days beginning before or after implantation of syngeneic colon cancer (Colon 38) in C57BL/6 mice. Tumor volume was determined throughout and histochemical analysis was also performed. Tumor tissue and serum vascular endothelial growth factor (VEGF) levels were measured. In vitro cell growth was assessed by the MTT assay. Both roxatidine and cimetidine significantly suppressed the growth of Colon 38 tumor implants. Histologic analysis revealed that such antagonists markedly increased necrotic areas and decreased the density of microvessels in tumor tissue. Both H2-receptor antagonists suppressed VEGF levels in tumor tissue and significantly decreased serum VEGF levels in Colon 38-bearing mice. Such drugs, however, failed to suppress in vitro growth of the cell line. In conclusion, both roxatidine and cimetidine were found to exert suppressive effects on the growth of colon cancer implants in mice by inhibiting angiogenesis via reducing VEGF expression. |
| Databáze: | OpenAIRE |
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