Magari Hirohito, Shimizu Yasuhito, Inada Ken-ichi, Enomoto Shotaro, Tomeki Tatsuji, Yanaoka Kimihiko, Tamai Hideyuki, Arii Kenji, Nakata Hiroya, Oka Masashi, Utsunomiya Hirotoshi, Tsutsumi Yutaka, Tsukamoto Tetsuya, Tatematsu Masae, Ichinose Masao
Second Department of Internal Medicine, Wakayama Medical University, Wakayama 641-0012, Japan.
Biochem Biophys Res Commun. 2005 Aug 26;334(2):606-12. doi: 10.1016/j.bbrc.2005.06.132.
The effect of the selective COX-2 inhibitor, etodolac, on Helicobacter pylori (Hp)-associated stomach carcinogenesis was investigated in Mongolian gerbils (MGs). Hp-infected MGs were fed for 23 weeks with drinking water containing 10 ppm N-methyl-N-nitrosourea. They were then switched to distilled water and placed on a diet containing 5-30 mg/kg/day etodolac for 30 weeks. We found that etodolac dose-dependently inhibited the development of gastric cancer, and no cancer was detected at a dose of 30 mg/kg/day. Etodolac did not affect the extent of inflammatory cell infiltration or oxidative DNA damage, but it significantly inhibited mucosal cell proliferation and dose-dependently repressed the development of intestinal metaplasia in the stomachs of Hp-infected MGs. These results suggest that COX-2 is a key molecule in inflammation-mediated stomach carcinogenesis and that chemoprevention of stomach cancer should be possible by controlling COX-2 expression or activity.
在蒙古沙鼠（MGs）中研究了选择性环氧化酶-2（COX-2）抑制剂依托度酸对幽门螺杆菌（Hp）相关胃癌发生的影响。给感染Hp的MGs饮用含10 ppm N-甲基-N-亚硝基脲的水23周。然后将它们换成蒸馏水，并给予含5-30 mg/kg/天依托度酸的饮食30周。我们发现依托度酸剂量依赖性地抑制胃癌的发生，在剂量为30 mg/kg/天时未检测到癌症。依托度酸不影响炎症细胞浸润程度或氧化性DNA损伤，但它显著抑制黏膜细胞增殖，并剂量依赖性地抑制感染Hp的MGs胃中肠化生的发展。这些结果表明COX-2是炎症介导的胃癌发生中的关键分子，并且通过控制COX-2的表达或活性有可能对胃癌进行化学预防。
