Inhibitory effect of cyclooxygenase-2 inhibitor on the metastasis of gastrointestinal tumor.

环氧合酶2抑制剂对胃肠道肿瘤转移的抑制作用

• 批准号: 11671226
• 负责人: KONNO Hiroyuki
• 金额: $ 1.79万
• 依托单位: Hamamatsu University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671226/
• 关键词: COX-2; Liver metastasis; Angiogenesis; apoptosis; COX-2; VEGF; Angiogenesis; Apoptosis; MVD; 微小環境; COX-1

Background. This study was designed to investigate the role of cyclooxygenase-2 (COX-2) in the liver metastasis and the effect of COX-2 inhibitor on metastasis of gastrointestinal tumor.Methods. Human colon cancer TK-4 was implanted subcutaneously (SC), peritoneally (PI) or orthotopically (on the surface of the cecum ; CI). The animals were sacrified 8 weeks after implantation and growing tumors were removed and examined. COX-1, -2 and VEGF mRNA level were determined by Northem Blotting analysis, and microvessel density (MVD) and apoptotic index were also examined. In addition, clinicopathological analysis was performed in 76 patients with colorectal cancer to clarify the role of COX-2 in the metastasis.Results. Liver metastasis developed most frequently in CI groups and the apoptotic index assessed by TUNEL staining was lowest in the CI group among the three groups. High expression of COX-2 had no connection with the density of ER-MP12-positive tumor microvesseles. Thirty-nine (51%) patients with colorectal cancer showed COX-2 over-expression, in whom liver metastasis developed more frequently than in those without overexpression (p<0.05). However, there was no significant difference in histological types, lymph node metastasis and peritoneal dissemination.Conclusions. These results suggest that COX-2 plays an important role in liver metastasis, and that high COX-2 expression may impair induction of apoptosis, but may not induce angiogenesis in colon cancer. COX-2 is one of target molecules for prevention of liver metastasis.

背景本研究旨在探讨环氧合酶-2（考克斯-2）在胃肠道肿瘤肝转移中的作用及考克斯-2抑制剂对胃肠道肿瘤转移的影响。将人结肠癌TK-4皮下（SC）、腹膜（PI）或原位（在盲肠表面; CI）植入。在植入后8周将动物冷冻，取出生长的肿瘤并进行检查。采用Northem Blotting法检测考克斯-1、-2和VEGF mRNA水平，并检测微血管密度（MVD）和凋亡指数。同时对76例大肠癌患者进行临床病理分析，探讨考克斯-2在大肠癌转移中的作用。CI组肝转移发生率最高，凋亡指数最低。考克斯-2的高表达与ER-MP 12阳性肿瘤微血管密度无关。考克斯-2过表达者39例（51%），肝转移率高于无表达者（p<0.05）。但在组织学类型、淋巴结转移和腹膜播散方面差异无统计学意义。这些结果表明，考克斯-2在肝转移中起着重要作用，高考克斯-2表达可能会损害诱导凋亡，但可能不会诱导血管生成在结肠癌。考克斯-2是预防肝转移的靶分子之一。

项目成果

Tuyoshi Shoji: "Orthotopic implantation of a colon cancer xenograft induces high expression of cyclooxygenase-2"(in preparation).

Tuyoshi Shoji：“结肠癌异种移植物的原位植入诱导环氧合酶-2 的高表达”（准备中）。