玉屏风散通过STAT3改善肝细胞肝癌免疫抑制微环境中NK细胞活性的机制研究  

Study of the mechanism of improving NK cell activity in the immunosuppressive microenvironment of hepatocellular carcinoma by Yupingfeng powder through STAT3

作　　者：袁琴[1] 姚霏[1] 刘敏[2] 张露蓉[1] YUAN Qin;YAO Fei;LIU Min;ZHANG Lurong(Suzhou Academy of Wumen Chinese Medicine,Suzhou Hosptial of Traditional Chinese Medicine,Jiangsu Province,Suzhou 215009;Department of Oncology,Suzhou Hosptial of Traditional Chinese Medicine,Jiangsu Province,Suzhou 215009)

机构地区：[1]江苏省苏州市中医医院吴门医派研究院,苏州215009 [2]江苏省苏州市中医医院肿瘤科,苏州215009

出　　处：《南通大学学报（医学版）》2023年第3期211-215,共5页Journal of Nantong University(Medical sciences)

基　　金：苏州市科技发展计划(民生科技)项目(SYS2020188,SS202083);江苏省卫生健康委医学科项目(M2020004);苏州市科技发展计划(医疗卫生创新)项目(SKJY2021132)。

摘　　要：目的:阐明玉屏风散在发挥抗肝细胞肝癌(hepatocellular carcinoma,HCC)效应作用中对自然杀伤细胞(natural killer cell,NK细胞)活性的影响及其机制。方法:采用Hepa1-6 HCC小鼠模型,造模后5 d,用玉屏风散药液(20、30、40 g生药/kg)进行灌胃给药,2周后处死小鼠。瘤体质量称重用于抑瘤率的计算;Western Blot检测肿瘤组织中信号转导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)/p-STAT3、程序性死亡因子1的配体(ligands for programmed death factor 1,PD-L1)的蛋白表达情况;ELISA法检测肿瘤组织中吲哚胺2,3-二氧化酶(indoleamine 2,3-dioxygenase,IDO)、TGF-β的表达情况;从癌旁组织中分选出NK细胞,流式细胞术和ELISA法检测NK细胞活性相关因子颗粒酶、穿孔素(Granzyme,Perforin)、IFN-γ的表达情况。结果:与模型组相比,不同剂量的玉屏风散(20、30、40 g生药/kg)均显著抑制HCC小鼠肿瘤的生长(均P<0.05),且呈剂量依赖型,其抑瘤率分别为21.48%、36.12%、49.56%;与模型组比,玉屏风散(20、30、40 g生药/kg)可抑制肿瘤组织中STAT3/p-STAT3、PD-L1的蛋白表达,以及IDO、TGF-β的分泌;且对癌旁组织中NK细胞活性相关因子Granzyme、Perforin、IFN-γ的表达有明显促进作用。结论:玉屏风散是通过抑制STAT3的活化来改善HCC免疫微环境中NK细胞的免疫活性,从而抑制HCC的发生发展。Objective:To clarify the effect and mechanism of Yupingfeng Powder on natural killer cell(NK cell)activity in exerting its anti hepatocellular carcinoma(HCC)effect.Methods:Hepa1-6 in situ HCC mouse model was used.Five days after modeling,Yupingfeng powder solution(20,30,40 g crude drug/kg)was administered by gavage,and the mice were killed after two weeks.Weigh the tumor mass for the calculation of tumor inhibition rate.Western Blot was used to detect the protein expression of signal transducer and activator of transcription 3(STAT3)/p-STAT3 and ligands for programmed death factor 1(PD-L1)in tumor tissue;ELISA method for detecting indoleamine 2,3-dioxygenase(IDO)and TGF-βin tumor tissue.NK cells were selected from the adjacent tissues,the NK cell activity related factors granzyme,perforin and IFN were detected by flow cytometry and the secretion of IFN-γwas detected by ELISA.Results:Compared with the model group,different concentrations of Yupingfeng powder(20,30,40 g crude drug/kg)significantly inhibited the growth of tumors in HCC mice in a dose-dependent manner(P<0.05),with tumor inhibition rates of 21.48%,36.12%,and 49.56%,respectively.Compared with the model group,Yupingfeng powder(20,30,40 g crude drug/kg)can inhibit the protein expression of STAT3/p-STAT3,PD-L1,as well as the secretion of IDO and TGF-βin tumor tissue.And for the expression of NK cell activity related factors Granzyme,Perforin,and IFN-γin adjacent cancer tissues has a significant promoting effect.Conclusion:Yupingfeng Powder can improve the immune activity of NK cells in the microenvironment of HCC by inhibiting the activation of signal transduction factor STAT3,thereby inhibiting the occurrence and development of HCC.

关 键 词：肝细胞肝癌 玉屏风散 自然杀伤细胞 信号转导和转录激活因子3 小鼠 

分 类 号：R735.7[医药卫生—肿瘤]