The role of COX-2 and the effect of COX-2 antagonist on the progression of intestinal metaplasia and gastric cancer

COX-2的作用及COX-2拮抗剂对肠化生和胃癌进展的影响

• 批准号: 18590704
• 负责人: SAKAMOTO Choitsu
• 金额: $ 2.49万
• 依托单位: Nippon 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: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590704/
• 关键词: COX-2; H.Dvlori; intestinal metanlasia; gastric cancer; selectice COX-2 antagonist; Cdx2; 選択的COX-2阻害薬; セレコキシブ; スナネズミ; h.pylori

The aim of this study was to see whether administration of celecoxib, a selective COX-2 inhibitor, prior to the appearance of intestinal metaplasia could prevent the development of gastric cancer in Helicobacter pylorrinfected Mongolian gerbils. The incidence of gastric adenocarcinoma was : controls, 0% (0/10) ; H. pylori group, 65% (13/20), and H. pylori plus celecoxib group, 23% (5/22 ; p < 0.05). Continuous celecoxib administration significantly reduced COX activity and COX-2 protein expression, Cdx2 and MUC2 protein immunoreactivity, and the extent of Alcian blue periodic acid-Schiff-positive intestinal metaplasia in H. pylori-infected gerbils. Celecoxib also induced apoptosis in these gerbils. Significant inhibition of Cdx2 expression in celecoxib group was also shown by Western blot analysis. Prior to the first appearance of intestinal metaplasia, timely administration of celecoxib prevents gastric cancer occurrence by disrupting the progression of intestinal metaplasia into gastric carcinoma through its inhibition of Cdx2 expression in H. pylori-infected Mongolian gerbils.

本研究的目的是观察在幽门螺杆菌感染的蒙古沙鼠出现肠上皮化生之前给予选择性考克斯-2抑制剂塞来昔布是否可以预防胃癌的发生。胃腺癌的发生率为：对照组，0%（0/10）; H. pylori组65%（13/20），H. pylori+塞来昔布组为23%（5/22 ; P < 0.05）。连续塞来昔布给药可显著降低H.感染幽门的沙鼠塞来昔布也诱导这些沙鼠的细胞凋亡。Western blot分析也显示塞来昔布组Cdx 2表达明显抑制。在肠上皮化生首次出现之前，及时给予塞来昔布可通过抑制H.感染幽门螺杆菌的蒙古沙鼠

项目成果

Clinical significance of prostaglandin E syntjiase expression in gastric cancer tissue

胃癌组织中前列腺素E合成酶表达的临床意义

• 发表时间: 2007
• 期刊: Human Pathology 38
• 作者: K.;Gudis;et. al.
• 通讯作者: et. al.

Clinical significance of prostaglandin E synthase expression in gastric cancer tissue

• DOI: 10.1016/j.humpath.2007.04.020
• 发表时间: 2007-12-01
• 期刊: HUMAN PATHOLOGY
• 影响因子: 3.3
• 作者: Gudis, Katya;Tatsuguchi, Atsushi;Sakamoto, Choitsu
• 通讯作者: Sakamoto, Choitsu

Chemoprevention of gastric cancer by celecoxib in Hpylori infected Mongolian gerbils

塞来昔布对幽门螺杆菌感染蒙古沙鼠胃癌的化学预防作用

• 发表时间: 2006
• 作者: S.;Futagami;et. al.
• 通讯作者: et. al.

Chemoprevention of gastric cancer by celecoxib in H.pylorr-infected Mongolian gerbils

塞来昔布对幽门螺杆菌感染的蒙古沙鼠胃癌的化学预防作用

• 发表时间: 2006
• 作者: S Futagami;et. al.
• 通讯作者: et. al.

Celecoxib inhibits Cdx2 expression and prevents gastric cancer in Helicobacter pylori-infected Mongolian gerbils

• DOI: 10.1159/000100503
• 发表时间: 2006-01-01
• 期刊: DIGESTION
• 影响因子: 3.2
• 作者: Futagami, Seiji;Suzuki, Kenji;Sakamoto, Choitsu
• 通讯作者: Sakamoto, Choitsu