Preliminary study of the mechanism of isolinderalactone inhibiting the malignant behavior of bladder cancer  

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作  者:Qun Wang Wenkai Xu Lu Ying Hongjin Shi Yuxin Sun Wei Feng Haole Xu Jun Xie Hairong Wei Zhao Yang Haifeng Wang 

机构地区:[1]Department of Urology,The Second Affiliated Hospital of Kunming Medical University,Kunming,China [2]Department of Urology,The Second People's Hospital of Xindu District,Chengdu,China [3]College of Life Science and Technology,Innovation Center of Molecular Diagnostics,Beijing University of Chemical Technology,Beijing,China [4]College of Life Science and Technology,Key Laboratory of Protection and Utilization of Biological Resources in Tarim Basin of Xinjiang Production and Construction Corps,Tarim University,Alar,Xinjiang,China

出  处:《Current Urology》2025年第1期49-58,共10页当代泌尿学(英文)

基  金:supported by the Fundamental Research Funds for the Central Universities(No.buctrc201910);Young Elite Scientists Sponsorship Program by Xinjiang Association for Science and Technology(2021);basic research program of Yunnan Science and Technology Department and Kunming Medical University(202101AY070001-144);the scientific research project of Education Department of Yunnan Province(No.2024Y231).

摘  要:Background:Isolinderalactone(ILL),extracted from the dried tubers of Linderae aggregate,has multiple functions,such as antioxidation,antitumor,and anti-infection effects.However,there have been fewstudies on ILL's antitumor role and no reports on its role in bladder cancer(BC).Materials and methods:Human BC cell lines T24 and EJ-1 were treated with different concentrations of ILL(0,10,20,50,100,200,400,600,800,and 1000μmol/L),and the cell proliferation inhibition rate was analyzed using the CCK-8 assay.The effect of ILL on T24 and EJ-1 cell cycle inhibition and apoptosis was examined using flow cytometry.Immunoblotting was used to detect the levels of apoptosis-related proteins,BAX,BAK1,and CYCS,in BC cells of the control and ILL-treated groups,and quantitative PCR experiments were performed to detect the apoptosis-related gene expression of CASP10,CYCS,BAX,BCL-2,CASP8,and BAK1.T24 and EJ-1 tumor-bearingmousemodels were established and divided into vehicle control,low-dose(10mg/kg)and high-dose(20mg/kg)groups,with 5 mice in each group.Hematoxylin and eosin staining and immunohistochemistry were used to detect changes in apoptosisrelated proteins in vivo.Results:The CCK-8 assay showed that in vitro,ILL significantly inhibited the proliferation of the T24 and EJ-1 BC cell lines.Flowcytometry and immunoblotting results showed that ILL increased mitochondrial permeability by upregulating proapoptotic proteins BAK1 and BAX,promoting CYCS release and significantly inducing cell cycle arrest at G0/G1 phase.In vivo,on day 25 of administration,tumor inhibition rates in T24 and EJ-1 tumor-bearing mice were up to 75.24% and 47.43%,respectively,in the ILL high-dose-treated and 71.58% and 43.89%,respectively,in the ILL low-dose-treated groups.Conclusions:Isolinderalactone controls BC progression by inducing apoptosis,suggesting that ILL may be an effective drug for the treatment of BC.

关 键 词:Bladder cancer Isolinderalactone Mitochondrial apoptosis 

分 类 号:R737.14[医药卫生—肿瘤]

 

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