The enzyme expressions of arachidonic acid cascade in rat colon carcinogenesis and modifying effects of chemopreventive agents

花生四烯酸级联酶在大鼠结肠癌发生中的表达及化学预防药物的调节作用

• 批准号: 07670237
• 负责人: YOSHIMI Naoki
• 金额: $ 1.54万
• 依托单位: GIFU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670237/
• 关键词: ARACHIDONIC ACID CASCADE; COLON CARCINOGENESIS; CHEMOPREVENTION; CYCLOOXYGENASE-2; PHOSPHOLIPASE A2; RATS; シクロオキシゲナーゼ

In this study, we examined the mRNA expression of phospholipase A2 and cyclooxygenase (COX)-2 on arachidonic acid cascade in rat colon carcinogenesis. Those expressions in carcinomas were significantly increased, and those in colon mucosa exposed with carcinogen were also induced. In addition, we examined the effects of NS-398, which is a selective COX-2 inhibitor, on the development of aberrant crypt foci (ACF), which is a pre-neoplastic lesion in rat colon carcinogenesis. As the results, NS-398 inhibited the formation of ACF.Now the long-term experiment for the chemoprevention of NS-398 is going on.[Methods] We used azoxymethane (AOM)-induced colon carcinogenesis model to examine the effect of NS-398,10mg/kg. And the expressions of COX-1 and -2, and cell proiferative potential were examined.[Results & Discussion] While the number of ACF in rats treated with AOM alone was 0.97(]SY.+-。[)0.32, that is rats treated with AOM and NS-398 (0.42(]SY.+-。[)0.14) was significantly decreased (P<0.001). The expressions of COX-1 and 2 in both groups treated with or without NS-398 were not significantly different. However, the cell proliferative potential in rats treated with NS-398 was decreased compared with that without NS-398. According to the results, COX inhibitors, which are related to the arachidonic acid cascade and non-steroid anti-inflammatory drugs (NAIDs), are considered the chemopreventive agents. Furthermore, as it has been reported that NSAIDs have potentials of apoptosis induction, the apoptotic mechanism of the inhibitory effect of NS-398 in colon carcinogenesis should be examined in future.

在本研究中，我们检测了大鼠结肠癌发生过程中磷脂酶A2和环氧合酶-2在花生四烯酸级联反应中的表达。它们在癌组织中的表达显著增加，在暴露于致癌物的结肠粘膜中也有表达。此外，我们还观察了选择性COX-2抑制剂NS-398对大鼠结肠癌前病变--异常隐窝病灶(ACF)形成的影响。[方法]采用偶氮甲烷(AOM)诱导的小鼠结肠癌模型，观察NS-398 10 mg/kg对小鼠结肠癌形成的影响。[结果与讨论]单用AOM组大鼠ACF数为0.97(SY.+-)。[]0.32，即AOM和NS-398(0.42()sy+-.)组大鼠。[)0.14)显著降低(P&lt；0.001)。NS-398组和NS-398组COX-1、COX-2表达无明显差异。然而，NS-398处理的大鼠细胞增殖能力低于未处理的大鼠。根据研究结果，与花生四烯酸级联反应相关的COX抑制剂和非类固醇抗炎药(NADS)被认为是化学预防药物。此外，由于已有报道表明非甾体抗炎药具有诱导细胞凋亡的潜能，因此NS-398抑制结肠癌发生的细胞凋亡机制有待于进一步研究。

项目成果

Masumi SUZUI et al.: "No involvement of Apc gene mutations in ulcerative colitis-associated rat colon carcinogenesis induced by 1-hydroxyanthraquinone and methylazoxymethanol acetate" Molecular Carcinogenesis. 20. 389-393 (1997)

Masumi SUZUI 等人：“Apc 基因突变与 1-羟基蒽醌和甲基偶氮甲醇乙酸酯诱导的溃疡性结肠炎相关的大鼠结肠癌无关”，分子癌变。

Yoshimi N.et al.: "Telomerase activity or normal tissues and neoplasms in rat colon carcinogenesis induced by methylazoxymetanol acetate and its difference from that of human・・・" Molecular Carcinogenesis. 16・1. 1-5 (1996)

Yoshimi N.等人：“乙酸甲基偶氮甲醇诱导的大鼠结肠癌发生中的端粒酶活性及其与人类的差异......”分子癌发生16·1。

Hirose Y.Yoshimi N et al.: "Early alterations of apoptosis and cell proliferation in azoxymethane induced rat colonic epithelium" Jpn.J.Cancer Res.87・6. 575-582 (1996)

Hirose Y.Yoshimi N 等：“氧化偶氮甲烷诱导的大鼠结肠上皮细胞凋亡和细胞增殖的早期改变”Jpn.J.Cancer Res.87·6（1996）。

Naoki Yoshimi et al.: "Telomerase activity of normal tissues and neoplasms in rat colon carcinogenesis induced by methylazoxymethanol acetate and its differnece…" Molecular Carcinogenesis. 16. 1-5 (1996)

Naoki Yoshimi 等人：“甲基偶氮甲醇乙酸酯诱导的大鼠结肠癌发生中正常组织和肿瘤的端粒酶活性及其差异……”分子癌发生。

Naoki YOSHIMI et al.: "The mRNA overexpression of inflammatory enzymes, phosphlipase A_2 and cyclooxygenase, in the large bowel mucosa and neoplasms of F344 rats treated with naturally occurring carcinogen, 1-hydroxyanthraquinone" Cancer Letters. 97. 75-8

Naoki YOSHIMI 等人：“在用天然致癌物 1-羟基蒽醌治疗的 F344 大鼠的大肠粘膜和肿瘤中，炎症酶、磷脂酶 A_2 和环氧合酶的 mRNA 过度表达”《癌症快报》。