A lipophilic statin, pitavastatin, suppresses inflammation-associated mouse colon carcinogenesis
A lipophilic statin, pitavastatin, suppresses inflammation-associated mouse colon carcinogenesis
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DOI：
10.1002/ijc.22976
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发表时间：
2007-11-15
影响因子：
6.4
通讯作者：
Tanaka, Takuji
中科院分区：
文献类型：
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作者：
Yasui, Yumiko;Suzuki, Rikako;Tanaka, Takuji
已知3-羟基-3-甲基戊二酰辅酶A （HMG-CoA）还原酶抑制剂可调节癌变。在这项研究中，我们研究了亲脂性HMG-CoA还原酶抑制剂匹伐他汀是否抑制炎症相关的小鼠结肠癌发生。将雄性CD-1 （ICR）小鼠一次性腹腔注射偶氮氧甲烷（AOM， 10 mg/kg体重），并在饮用水中添加2% （w/v）葡聚糖硫酸钠（DSS），持续7天。从停止DSS暴露后第1周开始，将含有吡伐他汀2种剂量水平（1 ppm和10 ppm）的实验饲粮喂给雄性CD-I （ICR）小鼠17周。在第5周、第10周和第20周评估饮食中匹伐他汀对结肠肿瘤发展的影响。在第20周时，两种剂量的匹伐他汀均能显著抑制结肠腺癌的多样性。此外，治疗显著降低了增殖细胞核抗原的阳性率，增加了结肠上皮恶性肿瘤的凋亡指数。治疗还降低了结肠黏膜的硝基酪氨酸阳性。因此，我们的研究结果表明，匹伐他汀通过调节粘膜炎症、氧化/亚硝化应激和细胞增殖，有效抑制结肠炎相关的结肠癌发生。(c) 2007 Wiley-Liss, Inc。
3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are known to modulate carcinogenesis. In this study, we investigated whether a lipophilic HMG-CoA reductase inhibitor pitavastatin suppresses inflammation-related mouse colon carcinogenesis. Male CD-1 (ICR) mice were initiated with a single intraperitoneal injection of azoxymethane (AOM, 10 mg/kg body weight) and promoted by 2% (w/v) dextran sodium sulfate (DSS) in drinking water for 7 days. The experimental diets containing pitavastatin at 2 dose levels (1 and 10 ppm) were fed to male CD-I (ICR) mice for 17 weeks, staring I week after the cessation of DSS exposure. The effects of dietary pitavastatin on colonic tumor development were assessed at Weeks 5, 10 and 20. Feeding with pitavastatin at both doses significantly inhibited the multiplicity of colonic adenocarcinoma at Week 20. Furthermore, the treatment significantly lowered the positive rates of proliferating cell nuclear antigen and increased the apoptotic index in the colonic epithelial malignancies. The treatment also reduced nitrotyrosine-positivity in the colonic mucosa. Our findings thus show that pitavastatin is effective in inhibiting colitis-related colon carcinogenesis through modulation of mucosal inflammation, oxidative/nitrosative stress, and cell proliferation. (c) 2007 Wiley-Liss, Inc.