Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, Indiana, United States of America.
PLoS One. 2012;7(10):e47873. doi: 10.1371/journal.pone.0047873. Epub 2012 Oct 30.
Epidemiological studies suggest that mushroom intake is inversely correlated with gastric, gastrointestinal and breast cancers. We have recently demonstrated anticancer and anti-inflammatory activity of triterpene extract isolated from mushroom Ganoderma lucidum (GLT). The aim of the present study was to evaluate whether GLT prevents colitis-associated carcinogenesis in mice.
METHODS/PRINCIPAL FINDINGS: Colon carcinogenesis was induced by the food-borne carcinogen (2-Amino-1-methyl-6-phenylimidazol[4,5-b]pyridine [PhIP]) and inflammation (dextran sodium sulfate [DSS]) in mice. Mice were treated with 0, 100, 300 and 500 mg GLT/kg of body weight 3 times per week for 4 months. Cell proliferation, expression of cyclin D1 and COX-2 and macrophage infiltration was assessed by immunohistochemistry. The effect of GLT on XRE/AhR, PXR and rPXR was evaluated by the reporter gene assays. Expression of metabolizing enzymes CYP1A2, CYP3A1 and CYP3A4 in colon tissue was determined by immunohistochemistry. GLT treatment significantly suppressed focal hyperplasia, aberrant crypt foci (ACF) formation and tumor formation in mice exposed to PhIP/DSS. The anti-proliferative effects of GLT were further confirmed by the decreased staining with Ki-67 in colon tissues. PhIP/DSS-induced colon inflammation was demonstrated by the significant shortening of the large intestine and macrophage infiltrations, whereas GLT treatment prevented the shortening of colon lengths, and reduced infiltration of macrophages in colon tissue. GLT treatment also significantly down-regulated PhIP/DSS-dependent expression of cyclin D1, COX-2, CYP1A2 and CYP3A4 in colon tissue.
Our data suggest that GLT could be considered as an alternative dietary approach for the prevention of colitis-associated cancer.
流行病学研究表明，蘑菇的摄入量与胃癌、胃肠道癌和乳腺癌呈负相关。我们最近证明了从蘑菇灵芝（GLT）中分离出的三萜提取物具有抗癌和抗炎活性。本研究旨在评估 GLT 是否可预防小鼠结肠炎相关的癌变。
方法/主要发现：通过食物源性致癌剂（2-氨基-1-甲基-6-苯基咪唑[4,5-b]吡啶[PhIP]）和炎症（葡聚糖硫酸钠[DSS]）在小鼠中诱导结肠癌变。小鼠每周用 GLT 治疗 3 次，剂量为 0、100、300 和 500mg/kg 体重，共 4 个月。通过免疫组化评估细胞增殖、细胞周期蛋白 D1 和 COX-2 的表达以及巨噬细胞浸润。通过报告基因检测评估 GLT 对 XRE/AhR、PXR 和 rPXR 的作用。通过免疫组化测定结肠组织中代谢酶 CYP1A2、CYP3A1 和 CYP3A4 的表达。GLT 处理显著抑制了 PhIP/DSS 暴露的小鼠中局灶性增生、异常隐窝灶（ACF）形成和肿瘤形成。Ki-67 在结肠组织中的染色减少进一步证实了 GLT 的抗增殖作用。PhIP/DSS 诱导的结肠炎症表现为大肠显著缩短和巨噬细胞浸润，而 GLT 治疗可防止结肠长度缩短，并减少结肠组织中巨噬细胞的浸润。GLT 处理还显著下调了 PhIP/DSS 依赖性结肠组织中细胞周期蛋白 D1、COX-2、CYP1A2 和 CYP3A4 的表达。
我们的数据表明，GLT 可被视为预防结肠炎相关癌症的一种替代饮食方法。
