Indomethacin suppresses growth of colon cancer via inhibition of angiogenesis in vivo.
AIM: It has been reported that regular consumption of nonsteroidal anti-inflammatory drugs like indomethacin decreases the incidence and mortality rate of a number of gastrointestinal cancers. We aimed to explore the efficacy and possible mechanisms of indomethacin on tumor growth and tumor angiogenesis of human colon cancer xenografts in nude mice. METHODS: MTT (thiazolyl blue) assay was used to assess the effect of indomethacin on cultured human colorectal cancer cell line HCT116. HCT116 cells were inoculated subcutaneously into BALB/c-nu/nu mice. After oral administration of indomethacin, 3 mg/kg.d for 4 wk, animals were sacrificed by cervical dislocation. Immunohistochemical staining was employed to determine the microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression in tumor tissues. RESULTS: Indomethacin, a non-selective COX inhibitor, significantly decreased the viability of HCT116 cells in a dose-dependent manner (P<0.05) with 50% inhibition at approximately 318.2+/-12.7 mumol/L. Growth of HCT116 cell tumor was significantly suppressed by indomethacin. The tumor volume was significantly decreased in the treated group (458.89+/-32.07 mm(3)) compared to the control group (828.21+/-31.59 mm(3)) (P<0.05). The MVD of the treated group (19.50+/-5.32) was markedly decreased compared to the control group (37.40+/-4.93) (P<0.001). The VEGF expression of the treated group (1.19+/-0.17) was obviously reduced as compared to the control group (1.90+/-0.48) (P<0.01). The decrease in MVD was positively correlated with the decrease of VEGF expression (r(s) = 0.714, P<0.05). We did not see gastrointestinal complications in the treated group and no differences were noted in the body weight of the mice between the two groups throughout the study (P>0.05). CONCLUSION: Indomethacin can significantly decrease the viability of cultured HCT116 cells and retard human colorectal HCT116 cell tumor growth via inhibiting tumor angiogenesis, which might be through reduction of VEGF expression.[1]References
- Indomethacin suppresses growth of colon cancer via inhibition of angiogenesis in vivo. Wang, H.M., Zhang, G.Y. World J. Gastroenterol. (2005) [Pubmed]
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