游离脂肪酸受体 (FFAR) 是 G 蛋白偶联受体，分为 4 种亚型； FFAR2 和 FFAR3 由短链脂肪酸激活，而 FFAR1 和 FFAR4 由长链脂肪酸激活。最近的研究表明 FFAR 可能参与结直肠癌 (CRC) 的病理生理学。在 CRC 患者中观察到 FFAR2 和 FFAR4 基因表达下降。我们研究的目的是在 CRC 体外和体内模型中评估选择性合成激动剂刺激 FFAR2 和 FFAR4 的抗癌作用。使用了 FFAR2 激动剂 4-CMTB 和 FFAR4 激动剂 GSK137647。与测试化合物孵育 48 小时后，使用 MTT 测定确定细胞活力（CCD 841 CoN 和 SW-480）。使用实时 qPCR 和蛋白质印迹来识别 FFAR 表达的变化。通过商业测试来表征迁移和入侵。通过氧化偶氮甲烷和葡聚糖硫酸钠诱导结肠炎相关结直肠癌 (CACRC) 小鼠模型。4-CMTB 和 GSK137647 显着降低癌细胞生长以及迁移和侵袭能力。两种合成化合物均可增加 SW-480 细胞中 FFAR2 和 FFAR4 的表达。 4-CMTB 和 GSK137647 都不影响 AOM/DSS 诱导的小鼠 CACRC 的进程，然而，4-CMTB 升高了小鼠组织中 FFAR2 蛋白的表达。我们提出，刺激 FFAR2 和 FFAR4 可能会抑制 CRC 细胞活力和迁移，并且CRC 中降低的 FFAR2 和 FFAR4 表达可以通过各自激动剂的治疗来恢复，这表明 CRC 治疗中新的有希望的药理学靶点。© 2024。作者。

Free fatty acid receptors (FFARs) are G protein-coupled receptors that divide into 4 subtypes; FFAR2 and FFAR3 are activated by short-chain fatty acids, while FFAR1 and FFAR4 - by long-chain fatty acids. Recent studies show the potential involvement of FFARs in the pathophysiology of colorectal cancer (CRC). A decrease in FFAR2 and FFAR4 gene expression is observed in patients with CRC. The aim of our study was to evaluate the anti-cancer effect of FFAR2 and FFAR4 stimulation by selective synthetic agonists in in vitro and in vivo models of CRC.FFAR2 agonist, 4-CMTB, and FFAR4 agonist, GSK137647 were used. Cell viability (CCD 841 CoN and SW-480) was determined after 48 h incubation with tested compounds using MTT assay. Real-time qPCR and Western Blot were used to identify changes in FFARs expression. Migration and invasion were characterized by commercially available tests. Colitis-associated CRC (CACRC) mouse model was induced by azoxymethane and dextran sodium sulfate.4-CMTB and GSK137647 significantly reduced cancer cell growth as well as migration and invasion capacities. Both synthetic compounds increased FFAR2 and FFAR4 expression in SW-480 cells. Neither 4-CMTB nor GSK137647 influenced the course of AOM/DSS-induced CACRC in mice, however, 4-CMTB elevated FFAR2 protein expression in mouse tissues.We presented that stimulation of FFAR2 and FFAR4 may inhibit CRC cell viability and migration and that the FFAR2 and FFAR4 expression decreased in CRC can be restored by treatment with respective agonists, indicating new promising pharmacological targets in CRC treatment.© 2024. The Author(s).