Hong-mei Wang1, Gui-ying Zhang. 1. Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha 410078, China.
Abstract
OBJECTIVE: To evaluate the efficacy of nonsteroidal anti-inflammatory drug indomethacin on tumor growth and microvessel angiogenesis of human colon cancer xenografts in nude mice. METHODS: Human colorectal cancer HCT116 cells were inoculated subcutaneously into BALB/c-nu/nu mice. After daily treatment with oral indomethacin for 4 weeks (3 mg.kg-1.d-1), the mice were sacrificed by cervical dislocation, and immunohistochemical staining was employed to determine microvessel density (MVD) and expression of vascular endothelial growth factors (VEGF) in the tumor tissues. RESULTS: Growth of HCT116 tumor was significantly suppressed by indomethacin. The tumor volume (mm3) was 458.89+/-32.07 in the treated group versus 828.21+/-31.59 in the control group (P<0.05). The MVDs of the treated and control groups were 19.50+/-5.32 and 37.40+/-4.93 respectively (P<0.001), and VEGF expressions were 1.19+/-0.17 and 1.90+/-0.48 (P<0.01), respectively. MVD and VEGF expression in the treated tumor tissue declined noticeably as compared with the controls. There was a positive correlation between the decrease of VEGF expression and that of MVD (rs=0.714, P<0.05). No obvious toxicity was observed in nude mice. CONCLUSION: Indomethacin can inhibit the growth of transplanted human colorectal HCT116 tumor in association with a significant reduction in angiogenesis, which may be achieved through inhibition of VEGF.
OBJECTIVE: To evaluate the efficacy of nonsteroidal anti-inflammatory drug indomethacin on tumor growth and microvessel angiogenesis of humancolon cancer xenografts in nude mice. METHODS:Humancolorectal cancer HCT116 cells were inoculated subcutaneously into BALB/c-nu/nu mice. After daily treatment with oral indomethacin for 4 weeks (3 mg.kg-1.d-1), the mice were sacrificed by cervical dislocation, and immunohistochemical staining was employed to determine microvessel density (MVD) and expression of vascular endothelial growth factors (VEGF) in the tumor tissues. RESULTS: Growth of HCT116 tumor was significantly suppressed by indomethacin. The tumor volume (mm3) was 458.89+/-32.07 in the treated group versus 828.21+/-31.59 in the control group (P<0.05). The MVDs of the treated and control groups were 19.50+/-5.32 and 37.40+/-4.93 respectively (P<0.001), and VEGF expressions were 1.19+/-0.17 and 1.90+/-0.48 (P<0.01), respectively. MVD and VEGF expression in the treated tumor tissue declined noticeably as compared with the controls. There was a positive correlation between the decrease of VEGF expression and that of MVD (rs=0.714, P<0.05). No obvious toxicity was observed in nude mice. CONCLUSION:Indomethacin can inhibit the growth of transplanted human colorectal HCT116 tumor in association with a significant reduction in angiogenesis, which may be achieved through inhibition of VEGF.