A High-Fat Diet Enhances Proliferation of Prostate Cancer Cells and Activates MCP-1/CCR2 Signaling
A High-Fat Diet Enhances Proliferation of Prostate Cancer Cells and Activates MCP-1/CCR2 Signaling
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DOI：
10.1002/pros.22531
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发表时间：
2012-12-01
期刊：
影响因子：
2.8
通讯作者：
Habuchi, Tomonori
中科院分区：
文献类型：
--
作者：
Huang, Mingguo;Narita, Shintaro;Habuchi, Tomonori
背景资料。包括高脂肪饮食(HFD)和高碳水化合物饮食(HCD)在内的饮食模式在前列腺癌的进展中起着重要作用。然而，这些饮食中哪一种对肿瘤进展的影响最大，其潜在的机制尚不清楚。方法：我们通过体内和体外模型研究了不同饮食对前列腺癌细胞生长和相关循环因子包括血清胰岛素、生长因子和炎症细胞因子的影响。结果：高脂饮食组前列腺癌LNCaP移植瘤的生长显著高于高脂饮食组和对照组(CD组，P=0.025；高脂饮食组和高脂饮食组，P=0.025；高脂饮食组和CD组，P=0.003)。高血压性肝病组血清单核细胞趋化蛋白-1水平显著高于高血压性肝病组和慢性阻塞性肺病组(P=0.024；高血压性肝病组P=0.033；高血压性肝病组P=0.001)。MCP-1受体CC趋化因子受体2(CCR2)的mRNA水平和活化Akt的表达均以HFD组最高。此外，HFD喂养的小鼠血清可促进两种PCa细胞的增殖，而CCR2基因敲除可抑制HFD诱导的LNCaP细胞的增殖。结论HFD对前列腺癌细胞生长的促进作用强于HCD或CD。MCP-1/CCR2信号可能参与了HFD诱导的前列腺癌的进展。前列腺癌72：1779-1788,2012。(C)2012年威利期刊公司。
BACKGROUND. Dietary patterns including high-fat diet (HFD) and high-carbohydrate diet (HCD) play an important role in prostate cancer progression. However, which of these diets have the greatest effect on tumor progression and its underlying mechanisms remains unclear.METHODS. We investigated the effects of different diets on prostate cancer cell growth and the relevant circulating factors including serum insulin, growth factors, and inflammatory cytokines using the in vivo and ex vivo model.RESULTS. The tumor growth of prostate cancer LNCaP xenograft was significantly higher in the HFD group than in the HCD and control diet (CD) groups (P = 0.01; HFD vs. HCD, P = 0.025; HFD vs. CD, P = 0.003). The mean level of the serum monocyte chemoattractant protein-1 (MCP-1) in the HFD group was significantly higher than that in the HCD and CD groups (P = 0.024; HFD vs. HCD, P = 0.033; HFD vs. CD, P = 0.001). The mRNA levels of CC chemokine receptor 2 (CCR2), which is an MCP-1 receptor, and the expression of activated Akt were the highest in the HFD group. Furthermore, serum from HFD-fed mice enhanced the proliferation of two PCa cells and CCR2 knockdown inhibited HFD-induced proliferation of LNCaP cells.CONCLUSIONS. An HFD enhanced prostate cancer cell growth more strongly than an HCD or CD. MCP-1/CCR2 signaling may be involved in an HFD-induced prostate cancer progression. Prostate 72: 1779-1788, 2012. (C) 2012 Wiley Periodicals, Inc.