Berberine restrained proliferation,invasion,and migration by targeting the glycogen synthase kinase 3β/β-catenin pathway in lung adenocarcinoma cells  

作　　者：Tenzin Wangmu Chenlu Li Guangsu Han Ping Yi 

机构地区：[1]Institute of Integrated Traditional Chinese and Western Medicine,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China [2]Department of Integrated Traditional Chinese and Western Medicine,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China

出　　处：《Oncology and Translational Medicine》2025年第2期58-72,共15页肿瘤学与转化医学(英文版)

基　　金：Supported by a grant from the National Natural Science Foundation of China(no.82174457)。

摘　　要：Background:Lung cancer is one of the deadliest cancers worldwide,creating a pressing need to develop novel drugs that inhibit oncogenic signaling pathways.Numerous studies have shown that berberine(BBR)has anti–lung cancer potential.We aimed to explore the anti–lung cancer effect of BBR and related mechanisms by targeting the glycogen synthase kinase 3β(GSK3β)/β-catenin pathway.Methods:Lung adenocarcinoma(LUAD)cells A549 and NCI-H1975 were treated with BBR.Results:Our results showed that BBR inhibited cell proliferation by decreasing c-Myc levels and induced cel cycle arrest in the G0/G1 phase by lowering cyclin D1 levels.BBR induced apoptosis by upregulating cleaved caspase 3 levels.BBR inhibited cell migration and invasion by decreasing N-cadherin levels.Furthermore,BBR upregulated the expression of GSK3βprotein and phospho-β-catenin proteins in the cytoplasm,while decreasing the expression ofβ-catenin protein.Next,LUAD cel s were exposed to CHIR-99021(a GSK3βinhibitor).This treatment led to an increase in c-Myc,cyclin D1,andβ-catenin levels at specific concentrations.BBR partially reversed the effects of CHIR-99021.Finally,LUAD cells were treated with CHIR-99021(4μmoL/L)combined with BBR(30 and 60μmoL/L)for 24 h.The expression of programmed death ligand 1(PD-L1)was assessed by Western blot analysis.Jurkat T cells and A549 cel s were cocultured for 24 h to examine the lactate dehydrogenase release rate.Results suggested that BBR suppressed the expression of PD-L1 and heightened the immune lethality of T cells.Conclusions:BBR suppressed the proliferative activity of LUAD cell lines A549 and NCI-H1975 in vitro,induced cell cycle arrest and cancer cel apoptosis in the G0/G1 stage,and repressed the migration and invasion of cancer cells.BBR reduced the PD-L1 protein expression and enhanced T-cell–mediated cytotoxicity.These effects appear to be related to BBR's regulation of the GSK3β/β-catenin pathway.

关 键 词：BERBERINE Glycogen synthase kinase 3β Lung adenocarcinoma Non‐small cell lung cancer Β-CATENIN 

分 类 号：R734.2[医药卫生—肿瘤]