Chemoprevention of Azoxymethane/Dextran Sodium Sulfate-Induced Mouse Colon Carcinogenesis by Freeze-Dried Yam Sanyaku and Its Constituent Diosgenin
Chemoprevention of Azoxymethane/Dextran Sodium Sulfate-Induced Mouse Colon Carcinogenesis by Freeze-Dried Yam Sanyaku and Its Constituent Diosgenin
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DOI：
10.1158/1940-6207.capr-10-0279
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发表时间：
2011-06-01
影响因子：
3.3
通讯作者：
Ohshima, Hiroshi
中科院分区：
文献类型：
--
作者：
Miyoshi, Noriyuki;Nagasawa, Tomoki;Ohshima, Hiroshi
研究了中药三芽苦及其主要成分山药皂苷元对结肠癌发生的影响。雄性ICR小鼠一次性腹腔注射偶氮甲烷(AOM)10 mg/kg体重，然后在饮用水中加入1.5%葡聚糖硫酸钠(DSS)，连续7天建立致癌模型。分别以20、100或500 mg/kg的剂量饲喂商品薯蓣皂苷元或三叶皂苷元，每公斤干重63.8+/-1.2 mg/kg，连续17周。与AOM/DSS治疗的小鼠相比，接受所有剂量薯蓣皂苷元或三亚苦素治疗的小鼠产生的结肠癌数量显著减少。AOM/DSS诱导的大鼠结肠粘膜溃疡和发育不良隐窝的发生率也明显减少，与AOM/DSS诱导的IL-1β等炎性细胞因子的表达明显减少一致。此外，给予AOM/DSS治疗的小鼠血清甘油三酯升高的水平在给予薯蓣皂苷元和三叶草的小鼠中往往会降低。基因芯片和实时逆转录聚合酶链式反应分析显示，给予薯蓣皂苷元可使脂蛋白脂肪酶的表达增加12倍，这可能是降低血清甘油三酯水平的原因之一。薯蓣皂苷元改变的其他基因包括与抗氧化应激反应和细胞凋亡相关的基因，如血红素加氧酶-1、超氧化物歧化酶-3和半胱氨酸天冬氨酸氨基转移酶-6。我们的结果表明，中药三叶草和各种山药的块茎作为食物可以预防人类结肠癌的发生。《癌症展望》；4(6)；924-34。(C)2011年AACR。
The effects of sanyaku, a traditional Chinese medicine [freeze-dried powder of the yam tuber (Dioscorea)], and its major steroidal saponin constituent, diosgenin, on colon carcinogenesis were investigated. Male ICR mice were subjected to a single intraperitoneal injection of azoxymethane (AOM; 10 mg/kg body weight) followed by administration of 1.5% dextran sodium sulfate (DSS) in drinking water for 7 days to establish carcinogenesis. Commercial diosgenin or sanyaku, which contained diosgenin at 63.8 +/- 1.2 mg/kg dry weight, was given in the diet at 20, 100, or 500 mg/kg for 17 weeks. Groups of mice that received diosgenin or sanyaku at all doses yielded significantly less number of colon tumors compared with the AOM/DSS-treated mice. Occurrence of colonic mucosal ulcer and dysplastic crypt induced by AOM/DSS treatment was also significantly decreased by the administration of diosgenin and sanyaku, which was in accordance with the significant reduction of AOM/DSS-mediated increases in expression of inflammatory cytokines such as IL-1 beta by diosgenin and sanyaku. Furthermore, elevated levels of serum triglyceride in the AOM/DSS-treated mice tended to be reduced in mice given diosgenin and sanyaku. Microarray and real-time reverse transcriptase PCR analyses revealed that diosgenin administration increased 12-fold the expression of lipoprotein lipase, which may contribute to reduced serum triglyceride levels. Other genes altered by diosgenin included those associated with antioxidative stress responses and apoptosis, such as heme oxygenase-1, superoxide dismutase-3, and caspase-6. Our results imply that the Chinese medicine sanyaku and the tubers of various yams containing diosgenin as food could be ingested to prevent colon carcinogenesis in humans. Cancer Prev Res; 4( 6); 924-34. (C) 2011 AACR.