Dose-dependent benefits of quercetin on tumorigenesis in the C3(1)/SV40Tag transgenic mouse model of breast cancer
Dose-dependent benefits of quercetin on tumorigenesis in the C3(1)/SV40Tag transgenic mouse model of breast cancer
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DOI：
10.4161/15384047.2014.955444
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发表时间：
2014-01-01
影响因子：
3.6
通讯作者：
Murphy, E. A.
中科院分区：
文献类型：
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作者：
Steiner, J. L.;Davis, J. M.;Murphy, E. A.
乳腺癌是女性癌症相关死亡的主要原因。栎素是一种被证明具有抗癌作用的黄酮醇。然而，很少有研究研究槲皮素对肿瘤形成的剂量依赖效应，也没有研究使用C3(1)/SV40标记乳腺癌小鼠模型。4周龄雌性C3(1)/SV40 TAG小鼠随机分为4组，每组15-16只，分别为对照组、低剂量(0.02%饲料)、中剂量(0.2%饲料)或高剂量(2%饲料)。每周两次评估肿瘤数量和体积，并在处死时(20周)进行评估。结果显示，饲料中添加的槲皮素对肿瘤数目和体积的影响呈倒U形；在处死时，中等剂量组最有效，与对照组(C3-CON：9.0+/-0.9；C3-0.2%：7.3+/-0.9)和(C3-CON：2061.8+/-977.0 mm(3)；和C3-0.2%：462.9+/-75.9 mm(3)相比，肿瘤数目和体积减少了20%和78%)。与高、低剂量组(C3-2%：1163.2+/-305.9 mm(3)；C3-0.02%：1401.5+/-555.6 mm(3))相比，中等剂量组的肿瘤体积和肿瘤数目(C3-2%：10.7+/-1.3 mm(3)；C3-0.02%：8.1+/-1.1 mm(3))减小。对C3-Con和C3-0.2%小鼠乳腺组织进行基因表达芯片分析，结果表明，经槲皮素处理后，31个基因表达下调，9个基因表达上调2倍以上(P<；0.05)。我们报告了这一新的发现，在人类乳腺癌转基因小鼠模型中，槲皮素对肿瘤数量和体积有明显的剂量依赖关系，这与与槲皮素治疗相关的特定基因表达信号有关。
Breast cancer is the leading cause of cancer related death in women. Quercetin is a flavonol shown to have anti-carcinogenic actions. However, few studies have investigated the dose-dependent effects of quercetin on tumorigenesis and none have used the C3(1)/SV40 Tag breast cancer mouse model. At 4 weeks of age female C3(1)/SV40 Tag mice were randomized to one of four dietary treatments (n = 15-16/group): control (no quercetin), low-dose quercetin (0.02% diet), moderate-dose quercetin (0.2% diet), or high-dose quercetin (2% diet). Tumor number and volume was assessed twice a week and at sacrifice (20 wks). Results showed an inverted 'U' dose-dependent effect of dietary quercetin on tumor number and volume; at sacrifice the moderate dose was most efficacious and reduced tumor number 20% and tumor volume 78% compared to control mice (C3-Con: 9.0 +/- 0.9; C3-0.2%: 7.3 +/- 0.9) and (C3-Con: 2061.8 +/- 977.0 mm(3); and C3-0.2%: 462.9 +/- 75.9 mm(3)). Tumor volume at sacrifice was also reduced by the moderate dose compared to the high and low doses (C3-2%: 1163.2 +/- 305.9 mm(3); C3-0.02%: 1401.5 +/- 555.6 mm(3)), as was tumor number (C3-2%: 10.7 +/- 1.3 mm(3); C3-0.02%: 8.1 +/- 1.1 mm(3)). Gene expression microarray analysis performed on mammary glands from C3-Con and C3-0.2% mice determined that 31 genes were down-regulated and 9 genes were up-regulated more than 2-fold (P < 0.05) by quercetin treatment. We report the novel finding that there is a distinct dose-dependent effect of quercetin on tumor number and volume in a transgenic mouse model of human breast cancer, which is associated with a specific gene expression signature related to quercetin treatment.