| First Author | Sunayama K | Year | 2002 |
| Journal | Carcinogenesis | Volume | 23 |
| Issue | 8 | Pages | 1351-9 |
| PubMed ID | 12151354 | Mgi Jnum | J:78064 |
| Mgi Id | MGI:2183255 | Doi | 10.1093/carcin/23.8.1351 |
| Citation | Sunayama K, et al. (2002) The role of cyclooxygenase-2 (COX-2) in two different morphological stages of intestinal polyps in APC(Delta474) knockout mice. Carcinogenesis 23(8):1351-9 |
| abstractText | The expression of COX-2 participates strongly in polyp formation of adenomatous polyposis coli (APC)-mutated mice. However, the mechanism of growth inhibition by COX-2 inhibition remains unclear. The aims of this study were to assess the role of COX-2 during the process of polyp formation in APC(Delta474) knockout mice. Starting at 4 weeks of age, the treated group (T group) were given a diet containing JTE-522, a selective COX-2 inhibitor, and the control group (C group) were given a control diet. At 12 weeks of age, mice were killed and polyps located in a proximal 10 cm of the small intestine were classified into two morphological stages: large adenomas (>300 microm in diameter) which lacked normal villous structure, and small adenomas (</=300 microm) covered with normal villous epithelia. In both classes, after counting the incidence, adenomas were examined for vascularity, expression of COX-2 and VEGF protein, labeling proliferating cell nuclear antigen (PCNA) and apoptosis with the TdT-mediated dUTP nick end labeling method, including expression of Bcl-2 and Bcl-X. JTE-522 significantly reduced the incidence of large adenomas, but not of small adenomas. Although it did not affect the proliferating potential of adenomas, the apoptosis index increased significantly in the T group accompanied by a reduction in Bcl-X expression in both small and large adenomas. In the C group, macrophages with both COX-2 and VEGF expression were observed in the submucosa of large adenomas, where some large vessels were also observed. JTE-522 inhibited the VEGF expression of these macrophages, resulting in a decrease in vascular area. In conclusion, macrophages with COX-2 and VEGF expression in the submucosal layer are responsible for angiogenesis in large adenomas, and a selective COX-2 inhibitor reduced the growth of adenoma mainly by its inhibitory effect on angiogenesis. |
