Advances in Brief Evaluation of Cyclooxygenase-2 Inhibitor for Potential Chemopreventive Properties in Colon Carcinogenesis '
Advances in Brief Evaluation of Cyclooxygenase-2 Inhibitor for Potential Chemopreventive Properties in Colon Carcinogenesis '
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环氧合酶 2 抑制剂在结肠癌发生中潜在化学预防作用的简要评价进展
DOI：
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发表时间：
2006
期刊：
影响因子：
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通讯作者：
Seibert
中科院分区：
文献类型：
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作者：
Bandaru;S. Reddy;Chinthalapally;V. Rao;Karen;Seibert
流行病学和实验室研究表明，结肠癌发生的风险与包括阿司匹林在内的非甾体类抗炎药的摄入量呈反比关系。非甾体类抗炎药抑制结肠癌发生的机制之一是通过抑制环氧合酶同工酶（考克斯-1和考克斯-2）产生的胰高血糖素。考克斯-2在结肠肿瘤中过表达。因此，选择性的考克斯-2抑制剂有可能作为化学预防剂。在一项双盲研究中，我们评估了SC-58635（一种考克斯-2抑制剂）和舒林酸（作为阳性对照）的化学预防特性，使用氧化偶氮甲烷诱导的结肠异常隐窝病灶（ACF）作为疗效的衡量标准。对5周龄雄性F344大鼠饲喂对照饲料（改良AIN-76 A）或含150或1500 ppm SC-58635、320 ppm舒林酸或1500 ppm安慰剂的实验饲料。两周后，将除溶媒（生理盐水）处理组中的动物外的所有动物皮下注射（s.c.注射氧化偶氮甲烷（15 mg/kg体重，每周一次，持续2周）。在16周龄时，处死所有大鼠并评价结肠的ACF。正如预期的那样，舒林酸的饮食给药抑制了ACF的发展，并减少了异常隐窝/病灶数量方面的隐窝多样性。给予1500 ppm SC-58635可抑制总ACF诱导和隐窝多样性约40 - 49%。我们发现SC-58635显著抑制结肠ACF形成和隐窝多样性，这加强了选择性考克斯-2抑制剂对结肠癌发生具有化学预防活性的假设。
Epidemlological and laboratory studies indicate an inverse relationship between the risk of colon cancer development and intake of nonsteroldal antiinflammatory agents, including aspirin. One of the mechanisms by which nonsteroidal antiinflammatory agents Inhibit colon carcInogenesis Is through the inhibition of prostaglandIn production by cyclooxygenase isozymes (COX-1 and COX-2). Overexpression of COX-2 has been oh served In colon tumors. Thus, selective inhibitors of COX-2 could poten tinily serve as chemopreventive agents. We have assessed the chemopre ventive properties of SC-58635, a COX-2 inhibitor, and of sulindac, as a positive control, In a double-blind study, using azoxymethane-induced colonic aberrant crypt foci (ACF) as a measure of efficacy. Five-week-old male F344 rats were fed the control diet (modified AIN-76A) or experi mental diets containing 150 or 1500 ppm SC-58635, 320 ppm sulindac, or 1500 ppm placebo. Two weeks later, all animals except those In vehicle (normal saline)-treated groups were s.c. injected with azoxymethane (15 mg/kg of body weight, once weekly for 2 weeks). At 16 weeks of age, all rats were sacrificed and colons were evaluated for ACF. As expected, dietary administration of sulindac suppressed ACF development as such and reduced crypt multiplicity In terms of number of aberrant crypts/ focus. Administration of 1500 ppm SC-58635 inhibited total ACF induc tion and crypt multiplicity by about 40—49%. Our finding that SC-58635 significantly suppressed colonic ACF formation and crypt multiplicity strengthens the hypothesis that a selective COX-2 Inhibitor possesses chemopreventive activity against colon carcinogenesis.
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影响因子：
29.4
作者：
DuBois, RN;Radhika, A;Entingh, AJ
通讯作者：
Entingh, AJ
影响因子：
11.2
作者：
C. Rao;D. Desai;B. Simi;Nalini Kulkarni;S. Amin;B. Reddy
通讯作者：
C. Rao;D. Desai;B. Simi;Nalini Kulkarni;S. Amin;B. Reddy
舒林酸（一种非甾体抗炎药）对结肠癌的化学预防。
影响因子：
11.2
作者：
Rao,CV;Rivenson,A;Simi,B;Zang,E;Kelloff,G;Steele,V;Reddy,BS
通讯作者：
Reddy,BS
影响因子：
11.2
作者：
L. Marnett
通讯作者：
L. Marnett