Beta-elemene inhibits the growth of KDM6A-null bladder cancer cells by suppressing the epithelial-mesenchymal transition  

作　　者：Ruonan Zhang Jiao Feng Yintao Zheng Qianru Zhu Bo Xiang Qibiao Wu Xinbing Sui 

机构地区：[1]The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health,Cancer Research Institute and School of Basic Medical Sciences,Central South University,Changsha 410008,Hunan,China [2]School of Pharmacy,Hangzhou Normal University,Hangzhou 311121,Zhejiang,China [3]Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines,Engineering Laboratory of Development and Application of Traditional Chinese Medicines,Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province,Hangzhou Normal University,Hangzhou 311121,Zhejiang,China [4]Department of Gastrointestinal and Pancreatic Surgery,Key Laboratory of Gastroenterology of Zhejiang Province,Zhejiang Provincial People’s Hospital,Hangzhou 310014,Zhejiang,China [5]School of Pharmaceutical Sciences,Zhejiang Chinese Medical University,Hangzhou 311402,Zhejiang,China [6]State Key Laboratory of Quality Research in Chinese Medicines,Faculty of Chinese Medicine,Macao University of Science and Technology,Macao 999078,China

出　　处：《Clinical Traditional Medicine and Pharmacology》2024年第2期15-24,共10页临床传统医学和药理学（英文）

基　　金：various sources,including Zhejiang Provincial Natural Science Foundation of China(grant No.LQ20H160013,LQ21H160038,and LY23H160026);the Science and Technology Development Fund,Macao SAR(File No.:0098/2021/A2).

摘　　要：Background:Bladder cancer is a highly prevalent and lethal malignant tumor characterized by frequent mutations/deletions of lysine-specific demethylase 6A(KDM6A),which is suggested to be a key event in cancer progression and metastasis.Beta-elemene has been shown to inhibit metastasis and growth of various tumors,but its effect on KDM6A-null bladder cancer cells remains unknown.Objective:This study aimed to investigate the potential and molecular mechanism ofβ-elemene in inhibiting the growth of KDM6A-null bladder cancer.Methods:This study examined the migration ability and viability of RT-4(KDM6A wild-type)and KU19-19(KDM6A-null)cell lines using wound healing assay and CCK-8,respectively.The inhibitory effect ofβ-elemene on KU19-19 cell migration was evaluated using transwell and immunofluorescence assays,and the expression of transfer-related proteins and genes was analyzed through western blot and qRT-PCR,respectively.Molecular docking was performed to predict the targeting ofβ-elemene,and the effects were confirmed in KDM6Aknockdown RT-4 cells.Finally,the therapeutic effect ofβ-elemene on bladder cancer was tested in animal models.Results:The study observed that loss of KDM6A increased bladder cancer cell migration,with KU19-19 exhibiting significantly stronger migration than RT-4.Further investigation revealed thatβ-elemene effectively inhibited KU19-19 cell migration,likely through targeting EZH2 as determined by molecular docking.Overexpression of KDM6A inhibited KU19-19 metastasis,while knockdown of KDM6A in RT-4 cells enhanced cell migration,which was reversed byβ-elemene treatment.Notably,in vivo testing revealed a significant suppression of KU19-19 cell growth withβ-elemene administered at a dosage of 100 mg/kg.Conclusion:β-elemene has the potential to suppress the growth of KDM6A-null bladder cancer by inhibiting epithelial-mesenchymal transition(EMT),which could make it a promising therapeutic option for patients with KDM6A-null bladder cancer.

关 键 词：Β-ELEMENE Lysine-specific demethylase 6A(KDM6A) Bladder cancer METASTASIS Epithelial-mesenchymal transition(EMT) 

分 类 号：R737.14[医药卫生—肿瘤]