Berberine enhances the anti-hepatocellular carcinoma effect of NK92-MI cells through inhibiting IFN-gamma-mediated PD-L1 expression

作     者：Kunyuan Wang Chengxin Gu Ganxiang Yu Jiaen Lin Zhilei Wang Qianting Lu Yangzhi Xu Dan Zhao Xiaofeng Jiang Weijian Mai Shiming Liu Hui Yang Kunyuan Wang;Chengxin Gu;Ganxiang Yu;Jiaen Lin;Zhilei Wang;Qianting Lu;Yangzhi Xu;Dan Zhao;Xiaofeng Jiang;Weijian Mai;Shiming Liu;Hui Yang

作者机构：Department of GastroenterologyThe Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdongChina Department of Hepatobiliary SurgeryThe Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdongChina Guangzhou Institute of Cardiovascular DiseaseThe Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdongChina 

出 版 物：《Liver Research》 (肝脏研究（英文）)

年 卷 期：2022年第6卷第3期

页      面：167-174页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：This study was supported by grants from the General Project of Guangdong Natural Science Foundation(2021A1515010795,2020A1515011255)to H.Yang the National Natural Science Foundation of China(no.81372634)to H.Yang the Medical Science and Technology Research Foundation of Guangdong Province(B2020114)to C.Gu the Guangzhou Health Science and Technology Project(20201A010054)to C.Gu 

主　　题：Berberine Hepatocellular carcinoma(HCC) NK92-MI cells Interferon gamma(IFN-g) Programmed cell death-ligand 1(PD-L1) 

摘      要：Background and aims:Berberine is one of the most promising clinically tested natural alkaloids,and immunotherapy using natural killer(NK)cells is a potentially effective treatment for hepatocellular carcinoma(HCC).This study aims to elucidate the effect of berberine on the anti-HCC effect of NK92-MI *** and methods:Human HCC SMMC-7721 and Hep3B cells were co-incubated with NK92-MI cells,berberine(60 or 80 mmol/L),or their combination for 36 *** evaluate the killing effect of NK92-MI cells on HCC cells,the release of lactate dehydrogenase(LDH)in HCC cells was *** anti-tumor effects of berberine,NK92-MI cells,and their combinations were evaluated by MTS,EdU,Tunel,and Western blot assays.A male BALB/c nude mouse subcutaneous tumor model was used to investigate the anti-HCC effect of berberine and NK92-MI cells in ***:The LDH assay showed that berberine enhanced the cytotoxicity of NK92-MI cells on HCC *** combination of berberine and NK92-MI cells demonstrated more obvious anti-HCC effect than did the berberine or NK92-MI single treatment in inhibiting cell proliferation and inducing apoptosis both in vitro and in ***,the expression of programmed cell death-ligand 1(PD-L1)in HCC cells was upregulated after co-culture with NK-92MI ***-L1 expression was knocked down,thereby inhibiting the proliferation and promoting apoptosis of HCC cells,and inhibited by berberine that blocked the secretion of interferon gamma(IFN-g),thereby enhancing the anti-tumor effect of NK92-MI ***:Current data show that the immunomodulatory role of berberine is to enhance the cytotoxic effect of NK92-MI cells and inhibit tumor immune escape by reducing the expression of *** study provides a rationale for the clinical application of berberine in combination with NK cells for the treatment of HCC.