Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Food Funct. 2024 Sep 16;15(18):9420-9433. doi: 10.1039/d4fo02346c.
The primary cause of mortality in colorectal cancer (CRC) patients is tumor metastasis. The epithelial-mesenchymal transition (EMT) stands out as a crucial factor promoting the metastasis of CRC. Previous findings suggest a potential inhibitory effect of docosahexaenoic acid (DHA) on CRC metastasis, but the precise mechanism remains unknown, this study aims to explore this issue. We assessed metastasis and recurrence, all-cause mortality, and cancer-related mortality rates according to DHA intake in independent CRC cohorts ( = 367) by survival analysis. The ability of DHA to block CRC cell migration and invasion was tested using transwell and wound-healing assays. The regulation of EMT marker genes in CRC by DHA was detected by quantitative real-time PCR (qPCR) and immunoblotting, and the effect of DHA on the TGF-β1/Smad signaling pathway was further investigated. These cellular findings were validated using a subcutaneous CRC mouse model. Survival analyses showed that lower DHA intake was associated with a higher risk of CRC metastasis and a poorer prognosis. experiments showed that DHA inhibits the TGF-β1/Smad signaling pathway and regulates downstream transcription factors, thereby reversing the EMT and inhibiting invasion and migration. In the mouse model, dietary DHA supplementation effectively increased blood DHA concentrations and inhibited CRC metastasis. Our study demonstrated that DHA inhibits CRC invasion and metastasis by inhibiting the TGF-β1/Smad signaling pathway. Increased intake of DHA among CRC patients may provide additional benefits to the prognosis of colorectal cancer.
结直肠癌（CRC）患者死亡的主要原因是肿瘤转移。上皮-间充质转化（EMT）是促进 CRC 转移的关键因素。先前的研究结果表明二十二碳六烯酸（DHA）可能抑制 CRC 转移，但确切的机制尚不清楚，本研究旨在探讨这一问题。我们通过生存分析评估了独立 CRC 队列（=367）中根据 DHA 摄入情况的转移和复发、全因死亡率和癌症相关死亡率。通过 Transwell 和划痕愈合实验测试了 DHA 阻断 CRC 细胞迁移和侵袭的能力。通过定量实时 PCR（qPCR）和免疫印迹检测 DHA 对 CRC 中 EMT 标记基因的调控，进一步研究了 DHA 对 TGF-β1/Smad 信号通路的影响。使用皮下 CRC 小鼠模型验证了这些细胞发现。生存分析表明，较低的 DHA 摄入与 CRC 转移风险增加和预后不良相关。实验表明，DHA 抑制 TGF-β1/Smad 信号通路并调节下游转录因子，从而逆转 EMT 并抑制侵袭和迁移。在小鼠模型中，饮食补充 DHA 有效增加了血液 DHA 浓度并抑制了 CRC 转移。我们的研究表明，DHA 通过抑制 TGF-β1/Smad 信号通路抑制 CRC 的侵袭和转移。CRC 患者增加 DHA 的摄入可能会为结直肠癌的预后提供额外的益处。
