Gevariya Nikunj, Besançon Marjorie, Robitaille Karine, Picard Valérie, Diabaté Lamoussa, Alesawi Anwar, Julien Pierre, Fradet Yves, Bergeron Alain, Fradet Vincent
Laboratoire d'Uro-Oncologie Expérimentale, Oncology Axis, Centre de Recherche du CHU de Québec-Université Laval, Québec, Quebec, Canada.
Faculté de Medicine, Université Laval, Québec, Quebec, Canada.
Prostate. 2019 Jan;79(1):9-20. doi: 10.1002/pros.23706. Epub 2018 Aug 2.
Several lines of evidence suggest effects of dietary fat on prostate cancer (PCa) development and progression. Targeting omega (ω)-3:ω6 fatty acids (FA) ratio could be beneficial against PCa by favorably modulating inflammation. Here, we studied the effects of ω3- and ω6-enriched diets on prostate tumor growth and inflammatory response in androgen-deprived and non-deprived conditions.
Immune-competent eugonadal and castrated C57BL/6 mice were injected with TRAMP-C2 prostate tumor cells and daily fed with ω3- or ω6-enriched diet. FA and cytokine profiles were measured in blood and tumors using gas chromatography and multiplex immunoassay, respectively. Immune cell infiltration in tumors was profiled by multicolor flow cytometry.
ω3-enriched diet decreased prostate TRAMP-C2 tumor growth in immune-competent eugonadal and castrated mice. Cytokines associated with Th1 immune response (IL-12 [p70], IFN-γ, GM-CSF) and eosinophil recruitment (eotaxin-1, IL-5, and IL-13) were significantly elevated in tumors of ω3-fed mice. Using in vitro experiments, we confirmed ω3 FA-induced eotaxin-1 secretion by tumor cells and that eotaxin-1 secretion was regulated by androgens. Analysis of immune cell infiltrating tumors showed no major difference of immune cells' abundance between ω3- and ω6-enriched diets.
ω3-enriched diet reduces prostate tumor growth independently of androgen levels. ω3 FA can inhibit tumor cell growth and induce a local anti-tumor inflammatory response. These findings warrant further examination of dietary ω3's potential to slow down the progression of androgen-sensitive and castrate-resistant PCa by modulating immune cell function in tumors.
多项证据表明膳食脂肪对前列腺癌（PCa）的发生和发展有影响。通过有利地调节炎症，靶向ω（ω）-3：ω6脂肪酸（FA）比例可能对PCa有益。在此，我们研究了富含ω3和ω6的饮食在雄激素剥夺和未剥夺条件下对前列腺肿瘤生长和炎症反应的影响。
将具有免疫活性的性腺功能正常和去势的C57BL/6小鼠注射TRAMP-C2前列腺肿瘤细胞，并每日喂食富含ω3或ω6的饮食。分别使用气相色谱法和多重免疫测定法测量血液和肿瘤中的FA和细胞因子谱。通过多色流式细胞术分析肿瘤中的免疫细胞浸润情况。
富含ω3的饮食可降低性腺功能正常和去势的具有免疫活性的小鼠的前列腺TRAMP-C2肿瘤生长。在喂食ω3的小鼠肿瘤中，与Th1免疫反应相关的细胞因子（IL-12 [p70]、IFN-γ、GM-CSF）和嗜酸性粒细胞募集相关的细胞因子（嗜酸性粒细胞趋化因子-1、IL-5和IL-13）显著升高。通过体外实验，我们证实肿瘤细胞分泌ω3 FA诱导的嗜酸性粒细胞趋化因子-1，且嗜酸性粒细胞趋化因子-1的分泌受雄激素调节。对浸润肿瘤的免疫细胞分析表明，富含ω3和ω6的饮食之间免疫细胞丰度没有重大差异。
富含ω3的饮食可降低前列腺肿瘤生长，且与雄激素水平无关。ω3 FA可抑制肿瘤细胞生长并诱导局部抗肿瘤炎症反应。这些发现值得进一步研究膳食ω3通过调节肿瘤中的免疫细胞功能来减缓雄激素敏感和去势抵抗性PCa进展的潜力。
