Chemopreventive effect of curcumin, a naturally occurring anti-inflammatory agent, during the promotion/progression stages of colon cancer.
Chemopreventive effect of curcumin, a naturally occurring anti-inflammatory agent, during the promotion/progression stages of colon cancer.
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发表时间：
1999-02
期刊：
影响因子：
11.2
通讯作者：
T. Kawamori;R. Lubet;V. Steele;G. Kelloff;Robert B. Kaskey;C. Rao;B. Reddy
中科院分区：
文献类型：
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作者：
T. Kawamori;R. Lubet;V. Steele;G. Kelloff;Robert B. Kaskey;C. Rao;B. Reddy
姜黄素源自姜黄根茎，具有抗氧化和抗炎特性，在起始和/或起始后阶段施用时，可抑制化学诱导的皮肤、前胃和结肠癌发生。本研究旨在研究在雄性 F344 大鼠结肠癌发生的促进/进展阶段（癌前阶段晚期）施用姜黄素时的化学预防作用。我们还研究了该药物对肿瘤细胞凋亡的调节作用。 5 周龄时，给雄性 F344 大鼠喂食不含姜黄素的对照饮食和含有 0.2% 合成姜黄素（纯度为 99.9%）的实验性 AIN-76A 饮食。在 7 周和 8 周龄时，对打算接受致癌物治疗的大鼠进行皮下注射。每周注射氧化偶氮甲烷（AOM），剂量为 15 毫克/公斤体重。指定用于促进/进展研究的动物在第二次 AOM 治疗后接受 AIN-76A 对照饮食 14 周，然后改用含有 0.2% 和 0.6% 姜黄素的饮食。 AOM 治疗后第 14 周，结肠中可能会出现癌前病变。他们继续接受各自的饮食，直到致癌物治疗后 52 周，然后被处死。结果证实了我们早期的研究，即在起始和起始后阶段施用 0.2% 姜黄素可显着抑制结肠肿瘤的发生。此外，在促进/进展阶段的饮食中施用0.2％和0.6％的合成姜黄素显着抑制了结肠非侵袭性腺癌的发病率和复数性，并且也强烈抑制了结肠侵袭性腺癌的复数性。事实上，对结肠腺癌的抑制是剂量依赖性的。与接受AOM和对照饮食的组中的结肠肿瘤相比，在起始阶段和起始后阶段以及整个促进/进展阶段给大鼠施用姜黄素增加了结肠肿瘤的细胞凋亡。因此，当姜黄素在致癌物治疗之前、期间和之后施用时以及仅在结肠癌发生的促进/进展阶段（从癌前阶段晚期开始）施用时，观察到姜黄素的化学预防活性。
Curcumin, derived from the rhizome of Curcuma longa L. and having both antioxidant and anti-inflammatory properties, inhibits chemically induced carcinogenesis in the skin, forestomach, and colon when it is administered during initiation and/or postinitiation stages. This study was designed to investigate the chemopreventive action of curcumin when it is administered (late in the premalignant stage) during the promotion/progression stage of colon carcinogenesis in male F344 rats. We also studied the modulating effect of this agent on apoptosis in the tumors. At 5 weeks of age, groups of male F344 rats were fed a control diet containing no curcumin and an experimental AIN-76A diet with 0.2% synthetically derived curcumin (purity, 99.9%). At 7 and 8 weeks of age, rats intended for carcinogen treatment were given s.c. injections of azoxymethane (AOM) at a dose rate of 15 mg/kg body weight per week. Animals destined for the promotion/progression study received the AIN-76A control diet for 14 weeks after the second AOM treatment and were then switched to diets containing 0.2 and 0.6% curcumin. Premalignant lesions in the colon would have developed by week 14 following AOM treatment. They continued to receive their respective diets until 52 weeks after carcinogen treatment and were then sacrificed. The results confirmed our earlier study in that administration of 0.2% curcumin during both the initiation and postinitiation periods significantly inhibited colon tumorigenesis. In addition, administration of 0.2% and of 0.6% of the synthetic curcumin in the diet during the promotion/progression stage significantly suppressed the incidence and multiplicity of noninvasive adenocarcinomas and also strongly inhibited the multiplicity of invasive adenocarcinomas of the colon. The inhibition of adenocarcinomas of the colon was, in fact, dose dependent. Administration of curcumin to the rats during the initiation and postinitiation stages and throughout the promotion/progression stage increased apoptosis in the colon tumors as compared to colon tumors in the groups receiving AOM and the control diet. Thus, chemopreventive activity of curcumin is observed when it is administered prior to, during, and after carcinogen treatment as well as when it is given only during the promotion/progression phase (starting late in premalignant stage) of colon carcinogenesis.