宿主 GPR120 在介导膳食 ω-3 脂肪酸抑制前列腺癌中的作用。
Role of Host GPR120 in Mediating Dietary Omega-3 Fatty Acid Inhibition of Prostate Cancer.
机构信息
Department of Urology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA.
Statistics Core, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA.
出版信息
J Natl Cancer Inst. 2019 Jan 1;111(1):52-59. doi: 10.1093/jnci/djy125.
BACKGROUND
GPR120, a G protein-coupled receptor for long-chain polyunsaturated fatty acids (FAs), mediates the anti-inflammatory effects of omega-3 (ω-3) FAs. We investigated whether host or tumor GPR120 plays a role in the anti-prostate cancer effects of ω-3 FAs.
METHODS
MycCap prostate cancer allografts were grown in immunocompetent wild-type (WT) and GPR120 knockout (KO) mice fed ω-3 (fish oil) or ω-6 (corn oil) diets. Immune cell infiltration was quantified by flow cytometry, and gene expression of immune cell markers in isolated tumor-associated macrophages (TAMs) was quantified by quantitative real-time polymerase chain reaction. Archived tissue from a fish oil intervention trial was used to correlate gene expression of GPR120 with cell cycle progression (CCP) genes and Ki67 index (n = 11-15 per group). All statistical tests were two-sided.
RESULTS
In WT mice (n = 7 per group), dietary ω-3 FAs decreased MycCap allograft tumor growth (mean [SD] final tumor volume ω-6 = 491 [437] mm3 vs ω-3 = 127 [77] mm3, P = .04), whereas in global GPR120KO mice (n = 7 per group) ω-3 FAs had no anticancer effects. Dietary ω-3 FAs inhibited GPR120KO-MycCaP allografts grown in WT mice (n = 8 per group; mean [SD] final tumor volume ω-6 = 776 [767] mm3 vs ω-3 = 36 [34] mm3, P = .02). Omega-3 FA treatment decreased the number of M2-like TAMs in tumor tissue and gene expression of M2 markers in isolated TAMs compared with ω-6 controls in WT (n = 7 per group) but not in GPR120KO mice (n = 7 per group). In human tissue, higher expression of stromal GPR120 correlated with greater reduction in expression of CCP genes in men with prostate cancer on a high-ω-3 diet (r = -.57, P = .04).
CONCLUSIONS
Host GPR120 plays a central role in the anti-prostate cancer effects of dietary ω-3 FAs. Future studies are required to determine if the anticancer effects of ω-3 FAs are mediated through inhibition of M2-like macrophages and if host GPR120 status predicts anticancer effects of dietary ω-3 FAs in men with prostate cancer.
背景
GPR120 是长链多不饱和脂肪酸（FAs）的 G 蛋白偶联受体，介导 ω-3（ω-3）FAs 的抗炎作用。我们研究了宿主或肿瘤 GPR120 是否在 ω-3 FAs 的抗前列腺癌作用中发挥作用。
方法
将 MycCap 前列腺癌同种异体移植物植入免疫功能正常的野生型（WT）和 GPR120 敲除（KO）小鼠中，这些小鼠分别喂食 ω-3（鱼油）或 ω-6（玉米油）饮食。通过流式细胞术定量免疫细胞浸润，通过定量实时聚合酶链反应定量分离的肿瘤相关巨噬细胞（TAMs）中免疫细胞标志物的基因表达。使用鱼油干预试验的存档组织将 GPR120 的基因表达与细胞周期进展（CCP）基因和 Ki67 指数相关联（每组 n=11-15）。所有统计检验均为双侧检验。
结果
在 WT 小鼠中（每组 n=7），饮食 ω-3 FAs 可降低 MycCap 同种异体移植物肿瘤生长（ω-6 组的最终肿瘤体积平均值[标准差]为 491[437]mm3，ω-3 组为 127[77]mm3，P=0.04），而在全身性 GPR120KO 小鼠中（每组 n=7），ω-3 FAs 则没有抗癌作用。饮食 ω-3 FAs 抑制了在 WT 小鼠中生长的 GPR120KO-MycCaP 同种异体移植物（每组 n=8；ω-6 组的最终肿瘤体积平均值[标准差]为 776[767]mm3，ω-3 组为 36[34]mm3，P=0.02）。与 ω-6 对照组相比，ω-3 FA 处理降低了 WT 小鼠（每组 n=7）肿瘤组织中 M2 样 TAMs 的数量和分离 TAMs 中 M2 标志物的基因表达，但在 GPR120KO 小鼠中（每组 n=7）则没有。在人类组织中，高表达的基质 GPR120 与接受高 ω-3 饮食的前列腺癌男性中 CCP 基因表达的更大降低相关（r=-0.57，P=0.04）。
结论
宿主 GPR120 在饮食 ω-3 FAs 的抗前列腺癌作用中起核心作用。需要进一步研究以确定 ω-3 FAs 的抗癌作用是否通过抑制 M2 样巨噬细胞介导，以及宿主 GPR120 状态是否预测饮食 ω-3 FAs 在前列腺癌男性中的抗癌作用。
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