解毒消癥饮抑制大肠癌细胞EMT及PD-L1表达相关研究  

Research relating to Jiedu Xiaozheng yin inhibiting the expressions of EMT and PD-L1 of colorectal cancer cells

作　　者：冯海兰 陈虹[1] 陈旭征[1] 魏丽慧[1] 方翌[1] 张竹青 曹治云[1] FENG Hai-lan;CHEN Hong;CHEN Xu-zheng(Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China)

机构地区：[1]福建中医药大学,福州350122

出　　处：《山西中医》2024年第3期53-56,共4页Shanxi Journal of Traditional Chinese Medicine

基　　金：陈可冀中西医结合发展基金项目(编号:CKJ2023001);福建省自然科学基金面上项目(编号:2021J01944)。

摘　　要：目的:从上皮间质转化(EMT)及免疫检查点配体-1 (PD-L1)角度探讨解毒消癥饮治疗大肠癌的生物学机制。方法:从TCGA数据库收集267例大肠癌患者相关数据,采用生物信息学分析大肠癌患者肿瘤特异性生存期与EMT和PD-L1的相关性;采用热图分析EMT相关转录因子与PD-L1之间的相关性,划痕实验检测解毒消癥饮对大肠癌细胞HCT-15和HCT-116愈合能力的影响,Western blot实验检测解毒消癥饮对大肠癌细胞HCT-15和HCT-116 EMT相关因子ZEB1、Snail、PD-L1、ZO-1和E-cadherin等蛋白表达的影响。结果:高表达EMT和高表达PD-L1显著降低了CRC患者生存期(P<0.01,P<0.05);PD-L1基因的表达与EMT相关因子基因(TWIST1、TWIST2、ZEB1、ZEB2、Snail1、Snail2、Vimentin等)表达呈正相关;解毒消癥饮干预后的大肠癌细胞愈合能力显著降低(P<0.05);同时,解毒消癥饮抑制肠癌细胞中EMT因子蛋白ZEB1、Snail、PD-L1的表达,上调ZO-1和E-cadherin蛋白的表达。结论:解毒消癥饮抑制肠癌EMT和免疫检查点配体PD-L1表达,对肠癌的抑制作用与抗肿瘤转移和调节免疫微环境相关。Objective:To approach the biological mechanism of Jiedu Xiaozheng yin(JXY)treating colorectal cancer(CRC)based on the perspective of epithelial-mesenchymal transition(EMT)and immune checkpoint ligand-1(PD-L1).Methods:The relevant data of 267 patients with CRC were collected from TCGA database.The correlativity between tumor-specific survival and EMT and PD-L1 of patients with CRC was analyzed by bioinformatics.The correlativity between EMT-related transcription factors and PD-L1 was analyzed by heat-map.The effect of JXY on the healing ability of CRC cells(HCT-15 and HCT-116)was detected by wound healing assay.The effect of JXY on the expressions of EMT-related factors ZEB1,Snail,PD-L1,ZO-1 and E-cadherin etc.protein in both cell lines(CRC cells HCT-15 and HCT-116)was detected by Western blot assay.Results:High expressions of EMT and PD-L1 shortened the survival of patients with CRC significantly(EMT,P<0.01;PD-L1,P<0.05).The expression of PD-L1 gene was positively correlated to the expression of gene of EMT-related factors(TWIST1,TWIST2,ZEB1,ZEB2,Snail1,Snail2,Vimentin,etc.),and high expression of PD-L1 was accompanied by high expression of EMT factor.The healing ability of JXY-intervened CRC cells was significantly decreased(P<0.05).Meanwhile,JXY inhibited the expression of EMT factor-related proteins ZEB1,Snail,PD-L1 in CRC cells,while up-regulated the expressions of ZO-1 and E-cadherin proteins.Conclusion:JXY inhibits the expressions of EMT and immune checkpoint ligand PD-L1 in colorectal cancer.Its inhibitory effect on colorectal cancer is related to anti-metastasis and regulation of immune microenvironment.

关 键 词：大肠癌 解毒消癥饮 EMT PD-L1 实验研究 

分 类 号：R735.34[医药卫生—肿瘤]