大麦若叶对溃疡性肠炎相关癌变的预防作用及机制初探

Preliminary mechanism of barley leaf in preventing colitis-associated colorectal tumorigenesis

大麦若叶(barley leaf,BL)对肠道健康具有潜在益处,但对结直肠癌的预防作用及机制尚未明确。为探究BL对结直肠癌的影响并阐述作用机制,研究分别建立了氧化偶氮甲烷/葡聚糖硫酸钠(azoxymethane/dextran sodium sulfate,AOM/DSS)诱导的结直肠癌小鼠模型和CT26移植瘤小鼠模型,研究发现BL明显减少了AOM/DSS诱导模型小鼠肿瘤结节数量但并不影响移植瘤小鼠肿瘤的生长。同时,通过蛋白印迹法,发现BL降低了结肠组织中重要结直肠癌致癌基因环氧合酶-2与表皮生长因子受体的蛋白表达水平;通过16S测序分析以及GC-MS分析,发现5%(质量分数)BL干预能够改善肠道菌群失调,使乙酸含量提升了2.53倍、丙酸3.63倍、丁酸3.81倍;通过细胞实验,发现乙酸钠、丙酸钠及丁酸钠可以抑制由表皮生长因子介导细胞恶性转化过程相关信号通路中p-AKT和p-ERK蛋白表达水平,从而明显抑制小鼠表皮细胞JB 6P+的恶性转化。综上所述,大麦若叶通过改善小鼠肠道菌群失调,提高部分短链脂肪酸的含量,下调肿瘤相关信号通路中关键蛋白的表达,抑制肿瘤细胞的增殖,进而缓解结直肠癌的发生和发展。

Barley leaf(BL)is potentially beneficial to intestinal health.But the impact on colorectal cancer(CRC)is unclear.To investigate the impact and mechanism,this study established two mouse models of CRC induced by azoxymethane(AOM)/dextran sodium sulfate(DSS)and CT26 subcutaneous injection.Results showed that BL could significantly reduce the AOM/DSS-induced tumorigenesis and had no impacts on transplanted tumor growth.Meanwhile,by means of western blot,16S analysis,and gas chromatography-mass spectrometer(GC-MS)analysis,this study found that 5%BL significantly decreased the expression of cyclooxygenase-2(COX-2)and epidermal growth factor receptor(EGFR)in the colon,improved dysbacteriosis,and increased the concentration of short-chain fatty acid(SCFA).Cell experiments showed that the sodium salt of SCFA could restrain the malignant transformation of epithelial cells by reducing the expression of p-AKT and p-ERK.In summary,barely leaf could attenuate the AOM/DSS-induced tumorigenesis via dysbacteriosis amelioration,increasing the concentration of part SCFA and down-regulating the expression of key proteins in tumor-related signaling pathways.