结肠直肠ALOX15作为EPA和DHA对结肠直肠癌发生的影响的主体因素的决定因素
bioRxiv : the preprint server for biology
|May 15, 2024
概括
埃可萨氨酸 (EPA) 和多可萨氨酸 (DHA) 对结直肠癌 (CRC) 的影响取决于宿主因子15-氧酶-1 (ALOX15). 肠道ALOX15表达确保EPA和DHA通过产生溶解素来抑制CRC.
科学领域:
- 胃肠病学 胃肠病学
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 埃可萨氨酸 (EPA) 和多可萨赫萨氨酸 (DHA),omega-3脂肪酸,对结直肠癌 (CRC) 产生了不一致的影响.
- 影响CRC中这些可变结果的潜在因素仍然不清楚.
- 来自EPA和DHA的溶解素通过抑制癌症进展至关重要的促炎信号通路而具有抗瘤性质.
研究的目的:
- 研究肠道ALOX15表达在调节EPA和DHA对CRC的影响中的作用.
- 为了确定ALOX15是否影响CRC模型中的EPA和DHA的溶解生成.
- 评估ALOX15对瘤微环境和CRC进展的影响.
主要方法:
- 利用在结肠上皮细胞中转基因表达ALOX15的小鼠模型.
- 在各种配方 (自由脂肪酸,乙烯,甘油三) 中使用EPA和DHA.
- 评估了CRC的发展,溶解素的产生,细胞因子/化学因子的表达和免疫细胞的透.
主要成果:
- EPA和DHA对CRC表现出不同的影响,受配方的影响.
- 肠道ALOX15转基因表达均抑制的CRC.
- ALOX15表达诱导了溶解素的产生,减少了前瘤性细胞因子 (IL-6,IL-1β,CCL2) 和改变了免疫细胞群 (减少了TAMs,增加了CD8 T细胞).
结论:
- 肠道ALOX15表达是决定EPA和DHA对CRC的抗癌作用的关键宿主因素.
- ALOX15促进了来自EPA和DHA的溶解蛋白的生成,从而显著抑制了结直肠癌的发生.
- 准ALOX15或增强resolvin生产可能是治疗CRC管理的治疗策略.
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