中国药业2025，Vol.34Issue(4)：41-48,8.DOI:10.3969/j.issn.1006-4931.2025.04.011
青蒿琥酯对肾母细胞瘤细胞恶性生物学行为的影响
Effect of Artesunate on the Malignant Biological Behavior of Wilms' Tumor Cells
摘要
Abstract
Objective To investigate the effect of artesunate(Art)on the malignant biological behavior of Wilms' tumor(WT)cells by regulating the Wnt/β-catenin signaling pathway.Methods WT tissue and its adjacent tissues were collected from 50 children who underwent surgical resection in the hospital from January 2020 to January 2021;the expression levels of Wnt1 and β-catenin proteins were detected by immunohistochemistry.The toxicity of 0,5,10,20,40,80,160 µmol/L Art on the human WT SK-NEP-1 cells was detected.SK-NEP-1 cells were divided into the control group(containing 0.1%DMSO culture medium),the low-,medium-,and high-dose Art groups(containing 10,20,40 µmol/L Art culture medium),and the LiCl group(containing 40 µmol/L Art+20 mmol/L LiCl culture medium);cell proliferation was detected by the MTT assay,cell viability was assessed by the plate cloning experiment,cell migration and invasion were detected by the Transwell chambers,cell apoptosis was detected by the flow cytometry,and the expression of proliferating cell nuclear antigen(PCNA),Bcl-2-associated X protein(Bax),and Wnt/β-catenin signaling pathway proteins was detected by the Western blot.BALB/c nude mice were randomly divided into the control group(equal volume of physiological saline),the Art group(40 mg/kg),and the LiCl group(20 mmol/kg LiCl+40 mg/kg Art),with eight mice in each group;SK-NEP-1 cell suspensions were subcutaneously injected into the right anterior axilla;one week later,physiological saline or drugs were intraperitoneally injected;the tumor mass and volume were measured,and the mRNA and protein expression of Wnt1,β-catenin,Ki-67,and Cleaved Caspase-3 in transplanted tumors were detected.Results Compared with those in adjacent cancer tissues,the positive expression rates of Wnt1 and β-catenin in WT tissues significantly increased(P<0.05).The cell survival rate was lower than 50%at 80,160 µmol/L Art.Compared with those in the control group,the cell absorbance values,expression levels of PCNA,Wnt1,β-catenin,c-nuclear protein-like gene,and Cyclin D1 proteins significantly decreased,the number of colony formation,migration and invasive cells significantly decreased,while the Bax protein expression level and cell apoptosis rate significantly increased in the low-,medium-and high-dose Art groups(P<0.05).The in vivo experiment showed that compared with those in the control group,the tumor mass and volume in the high-dose Art group significantly decreased,the expression levels of Wnt1,β-catenin,Ki-67 mRNA and protein in the transplanted tumors significantly decreased,the expression levels of Cleaved Caspase-3 mRNA and protein significantly increased(P<0.05).Compared with those in the high-dose Art group,the above indicators in the LiCl group were worse(P<0.05).Conclusion Art may inhibit the malignant behavior of WT cells by suppressing the activation of the Wnt/β-catenin signaling pathway.关键词
青蒿琥酯/Wnt/β-catenin信号通路/肾母细胞瘤/细胞增殖/细胞迁移/细胞凋亡Key words
artesunate/Wnt/β-catenin signaling pathway/Wilms' tumor/cell proliferation/cell migration/cell apoptosis分类
医药卫生引用本文复制引用
房彦乐,鲁雨博,魏建新,高宇光,郎兴,马新生,李静涛..青蒿琥酯对肾母细胞瘤细胞恶性生物学行为的影响[J].中国药业,2025,34(4):41-48,8.基金项目
河北省中医药管理局科研计划项目[2024195]. （）
