Indomethacin suppresses growth of colon cancer via inhibition of angiogenesis in vivo.
OBJECTIVE
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).


CONCLUSIONS
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.
Wang
Hong-Mei
HM
Department of Gastroenterology, Xiangya Hospital of Central South University, Changsha 410078, Hunan Province, China.
Zhang
Gui-Ying
GY
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008833:Microcirculation / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A; D007213:Indomethacin