A selective cyclooxygenase 2 inhibitor suppresses the growth of H-ras-transformed rat intestinal epithelial cells.
A selective cyclooxygenase 2 inhibitor suppresses the growth of H-ras-transformed rat intestinal epithelial cells.
复制标题
选择性环氧合酶 2 抑制剂可抑制 H-ras 转化的大鼠肠上皮细胞的生长。
DOI：
10.1016/s0016-5085(97)70007-6
复制
发表时间：
1997
期刊：
影响因子：
29.4
通讯作者：
Beauchamp,RD
中科院分区：
文献类型：
--
作者：
Sheng,GG;Shao,J;Sheng,H;Hooton,EB;Isakson,PC;Morrow,JD;CoffeyJr,RJ;DuBois,RN;Beauchamp,RD
背景与目的85%的结直肠癌组织中存在环氧化酶2（cyclooxygenase 2，考克斯-2）的组成型表达。Ras突变在50%的结直肠腺癌中发现。本研究的目的是确定考克斯-2在ras诱导的大鼠肠上皮（RIE）细胞转化中的作用。方法通过细胞计数来确定细胞生长。考克斯-2的表达采用北方和西方分析。对于致瘤性测定，将细胞接种到无胸腺裸鼠的背部皮下组织中。考克斯-2在RIE-Ras细胞中的表达在信使RNA（9倍）和蛋白质（12倍）水平上均增加。RIE-Ras细胞中前列腺素I2水平升高2.15倍。血清剥夺进一步增加RIE-Ras细胞中考克斯-2表达3.8倍。用选择性考克斯-2拮抗剂（SC 58125）处理通过抑制细胞增殖和诱导凋亡来抑制RIE-Ras细胞的生长。SC-58125处理使基质胶中殖民地形成减少83.0%。腹腔注射SC-58125 4周后，裸鼠RIE-Ras肿瘤生长抑制率为60.3%。结论考克斯2过表达可能与ras转化的肠上皮细胞的致瘤性有关。选择性抑制考克斯-2活性可抑制ras转化的肠上皮细胞的生长并诱导凋亡。（胃肠病学1997年12月;113（6）：1883-91）
BACKGROUND & AIMSConstitutive expression of cyclooxygenase 2 (COX-2) has been found in 85% of colorectal cancers. Ras mutations are found in 50% of colorectal adenocarcinomas. The aim of this study was to determine the role of COX-2 in ras-induced transformation in rat intestinal epithelial (RIE) cells.METHODSCell growth was determined by cell counts. The expression of COX-2 was examined by Northern and Western analyses. For tumorigenicity assays, cells were inoculated into dorsal subcutaneous tissue of athymic nude mice. DNA-fragmentation assays were performed to detect apoptosis.RESULTSThe expression of COX-2 was increased in RIE-Ras cells at both messenger RNA (9-fold) and protein (12-fold) levels. Prostaglandin I2 levels were elevated 2.15-fold in RIE-Ras cells. Serum deprivation further increased COX-2 expression 3.8-fold in RIE-Ras cells. Treatment with a selective COX-2 antagonist (SC58125) inhibited the growth of RIE-Ras cells through inhibition of cell proliferation and by induction of apoptosis. SC-58125 treatment reduced the colony formation in Matrigel by 83.0%. Intraperitoneal administration of SC-58125 suppressed RIE-Ras tumor growth in nude mice by 60.3% in 4 weeks. SC-58125 treatment also induced apoptosis in RIE-Ras cells as indicated by increased DNA fragmentation.CONCLUSIONSOverexpression of COX-2 may contribute to tumorigenicity of ras-transformed intestinal epithelial cells. Selective inhibition of COX-2 activity inhibits growth of ras-transformed intestinal epithelial cells and induces apoptosis. (Gastroenterology 1997 Dec;113(6):1883-91)