Role of COX-2 in the development of gastric tumor by Helicobacter Pylori

COX-2在幽门螺杆菌胃肿瘤发生中的作用

• 批准号: 14570502
• 负责人: ARAI Shin
• 金额: $ 1.92万
• 依托单位: Saitama Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570502/
• 关键词: COX-2; gastric hyperplastic polyp; gastric adenoma; Helicobacter pylori; prostaglandin; cDNA microarray; angiogenesis; carcinogenesis; COX-2; 胃癌

Expression of COX-2 in human gastric mucosa with or without Helicobacter Pylori (H.pylori) Infection was immunohistochemically investigated. H.pylori infection induced the accumulation of neutrophils but not COX-2 expression in normal gastric mucosa. In the next step. Gastric pylyps were studied. COX-2 was strongly expressed in mesenchymal cells under the surface of gastric hyperplastic polyps. However, COX-2 was only weekly expressed in gastric adenomas Microvessel density was significantly collated with the expression of COX-2. These results suggest that COX-2 is related to the growth of hyperplastic polyp but not adenoma in stomach.Since COX-2 was mainly expressed in mesenchymal cells, it is postulated that prostaglandins (PGs, product of COX-2) accelerate growth of tumors and further cancer formation. This step may be mediated by angiogenesis. Therefore, we investigated the effect of PGs on VEGF production. PGs dramatically increased VEGF production by U-937 cells, A model of human macrophages. Changes of gene expression was studied by cDNA microarray using these cells. Among 10,000 genes, several of them were increased or decreased after treatment with PGs. Meaning of each gene will be studiedThis results suggest that in human gastric hyperplastic polyp H.pylori induces COX-2 expression in mesenchymal cells and promotes angiogenesis, development of tumor, and cancer formation.

采用免疫组化方法研究了幽门螺杆菌（Helicobacter Pylori，H.pylori）感染和正常胃粘膜中考克斯-2（COX-2）的表达。幽门螺杆菌感染诱导中性粒细胞聚集，但不诱导考克斯-2表达。下一步。研究胃幽门。考克斯-2在胃增生性息肉表面下的间充质细胞中呈强表达。然而，考克斯-2仅在胃腺瘤中每周表达。微血管密度与考克斯-2的表达显著相关。这些结果表明，考克斯-2与胃增生性息肉的生长有关，而与腺瘤无关，由于考克斯-2主要表达于间充质细胞，推测考克斯-2的产物--前列腺素（PGs）可促进肿瘤的生长和癌变。这一步骤可能是由血管生成介导的。因此，我们研究了PG对VEGF产生的影响。PG显著增加了U-937细胞（一种人类巨噬细胞模型）的VEGF产生。利用基因芯片技术研究细胞基因表达的变化。在10，000个基因中，有几个在PG处理后增加或减少。结果提示，在人胃增生性息肉中，H.pylori诱导间充质细胞表达考克斯-2，促进血管生成，促进肿瘤的发生发展，促进癌的形成。

项目成果

Bamba H, Ota S: "Recent.Res.Devel.Biophys.Biochem.(共著)"A.Gayathri. 568(345-362) (2003)

Bamba H、Ota S：“Recent.Res.Devel.Biophys.Biochem.（合著者）”A.Gayathri。568（345-362）（2003）

Bamba H, Ota S, Arai S, et al.: "Expression of cyclooxygenase-2 in human hyperplastic gastric polyps."J Exp Clin Cancer Res. 22. 425-430 (2003)

Bamba H、Ota S、Arai S 等人：“人增生性胃息肉中环氧合酶 2 的表达”。J Exp Clin Cancer Res。

Bamba H, Ota S, Kato A, et al.: "Effect of rebamipide on prostaglandin receptors-mediated increase of inflammatory cytokine production by macrophages."Aliment Pharmacol Ther.. Suppl 1. 113-118 (2003)

Bamba H、Ota S、Kato A 等人：“瑞巴派特对前列腺素受体介导的巨噬细胞炎症细胞因子产生增加的影响。”Aliment Pharmacol Ther.. Suppl 1. 113-118 (2003)

Bamba H, Ota S, Aral S, et al.: "Expression of cyclooxygenase-2 in human hyperplastic gastric polyps"J Exp Clin Cancer Res. 22. 425-430 (2003)

Bamba H、Ota S、Aral S 等人：“人增生性胃息肉中环氧合酶 2 的表达”J Exp Clin Cancer Res。

Bamba H, Ota S, Kato A, et al.: "Effect of rebamipide on prostaglandin receptors mediated increase of inflammatory cytokine production by macrophages"Alient Pharmacol Ther.. Suppl1. 113-118 (2003)

Bamba H、Ota S、Kato A 等人：“瑞巴派特对前列腺素受体介导的巨噬细胞炎症细胞因子产生增加的影响”Alient Pharmacol Ther.. Suppl1。