Endogenous n-3 polyunsaturated fatty acids prevent azoxymethane-induced colon tumorigenesis in mice fed a high-fat diet
Endogenous n-3 polyunsaturated fatty acids prevent azoxymethane-induced colon tumorigenesis in mice fed a high-fat diet
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内源性 n-3 多不饱和脂肪酸可预防氧化偶氮甲烷诱导的高脂饮食小鼠结肠肿瘤发生
DOI：
10.1016/j.jff.2018.07.042
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发表时间：
2018-09
影响因子：
5.6
通讯作者：
Xiao Hong Zhang
中科院分区：
文献类型：
--
作者：
An Jun Yao;Jia Hui Chen;Yan Xu;Zhuang Wei Zhang;Zu Quan Zou;Hai Tao Yang;Qi Hang Hua;Jin Shun Zhao;Jing Xuan Kang;Xiao Hong Zhang
文献表明高脂饮食(HFD)在肿瘤发生中的重要作用，但其潜在的机制仍然知之甚少。这项研究评估了n-3多不饱和脂肪酸(PUFAs)对HFD增强的结肠肿瘤的保护作用及其潜在机制。WT小鼠饲喂正常脂肪饲料或高脂饲料，Fat-1小鼠高脂饲料喂养22 周。在1-6周内，所有小鼠每周给药一次。HFD显著增强AOM诱导的WT小鼠的结肠癌形成；然而，Fat-1小鼠的肿瘤发生率和多发性显著降低。高脂饮食诱导的肿瘤发生涉及炎症信号通路的激活，包括肿瘤坏死因子-α/核因子-κB、IL-6/STAT3及其下游的β通路和与癌细胞增殖相关的β-连环蛋白/c-myc通路的上调。N-3多不饱和脂肪酸抑制了结肠癌的发展，减轻了前述炎症途径和致癌信号的变化。我们为n-3多不饱和脂肪酸作为潜在的结肠癌化学预防药物的作用提供了实验证据。
Literature suggests important roles of a high-fat diet (HFD) in tumour development, but the underlying mechanisms remain poorly understood. This study assessed the protective effect of n-3 polyunsaturated fatty acids (PUFAs) on HFD-enhanced colon tumours and the underlying mechanism. WT mice were fed a normal fat diet or HFD and Fat-1 mice were fed a HFD for 22 weeks. For weeks 1–6, all mice were intraperitoneally administered AOM weekly. HFD significantly enhanced AOM-induced colon tumorigenesis in WT mice; however, tumour incidence and multiplicity were markedly lower in Fat-1 mice. HFD-triggered tumour development involved the activation of inflammatory signalling pathways, including TNF-α/NF-κB, IL-6/STAT3, and downstream NLRP3/IL-1β pathways and upregulation of β-catenin/c-myc pathway, which is associated with cancer cell proliferation. n-3 PUFAs inhibited colon tumour development and mitigated the changes to the aforementioned inflammatory pathways and oncogenic signalling. We provide experimental evidence for the role of n-3 PUFAs as potential chemopreventive agents against colon cancer.
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影响因子：
2.8
作者：
Shankar, Eswar;Vykhovanets, Eugene V.;Vykhovanets, Olena V.;MacLennan, Gregory T.;Singh, Rajesh;Bhaskaran, Natarajan;Shukla, Sanjeev;Gupta, Sanjay
通讯作者：
Gupta, Sanjay
影响因子：
5.1
作者：
Cortez, Mayara;Carmo, Luciana Simao;Fock, Ricardo Ambrosio
通讯作者：
Fock, Ricardo Ambrosio
影响因子：
6.4
作者：
Han, Young-Min;Park, Jong-Min;Hahm, Ki Baik
通讯作者：
Hahm, Ki Baik
影响因子：
4.7
作者：
Suzuki, R;Kohno, H;Tanaka, T
通讯作者：
Tanaka, T
影响因子：
11.2
作者：
E. Lemmer;Yingbei Chen;S. Yea;E. Wurmbach;M. Schwartz;G. Khitrov;A. Villanueva;G. Narla;S. Waxman;S. Friedman;J. Llovet
通讯作者：
E. Lemmer;Yingbei Chen;S. Yea;E. Wurmbach;M. Schwartz;G. Khitrov;A. Villanueva;G. Narla;S. Waxman;S. Friedman;J. Llovet