Doxycycline Hydrochloride Regulates Cytoskeletal Rearrangement and Epithelial-To-Mesenchymal Transition in Malignant Rhabdoid Tumour of the Kidney
作者全名："Zhanghuang, Chenghao; Zhang, Zhaoxia; Mi, Tao; Wang, Jinkui; Jin, Liming; Liu, Jiayan; Li, Maoxian; Li, Mujie; Wu, Xin; Wang, Zhang; He, Dawei"
作者地址："[Zhanghuang, Chenghao; Zhang, Zhaoxia; Mi, Tao; Wang, Jinkui; Jin, Liming; Liu, Jiayan; Li, Maoxian; Li, Mujie; Wu, Xin; Wang, Zhang; He, Dawei] Chongqing Med Univ, Chongqing Higher Inst Engn Res Ctr Childrens Med B, Natl Clin Res Ctr Child Hlth & Disorders, Dept Urol,Childrens Hosp, Chongqing, Peoples R China; [Zhanghuang, Chenghao] Kunming Med Univ, Kunming Childrens Hosp, Yunnan Prov Clin Res Ctr Childrens Hlth & Dis, Dept Urol, Kunming, Peoples R China"
通信作者："He, DW (通讯作者)，Chongqing Med Univ, Chongqing Higher Inst Engn Res Ctr Childrens Med B, Natl Clin Res Ctr Child Hlth & Disorders, Dept Urol,Childrens Hosp, Chongqing, Peoples R China."
来源：BIOMED RESEARCH INTERNATIONAL
ESI学科分类：BIOLOGY & BIOCHEMISTRY
WOS号：WOS:000889102200002
JCR分区：Q3
影响因子：3.246
年份：2022
卷号：2022
期号：
开始页：
结束页：
文献类型：Article
关键词：
摘要："Objective. As a highly malignant tumour, malignant rhabdoid tumours of the kidney (MRTK) are prone to metastasis and invasion, while tumour metastasis and invasion are inseparable from matrix metalloproteinases (MMPs) and epithelial-mesenchymal transformation (EMT). Moreover, the key to EMT is remodelling of the cytoskeleton. Therefore, our study is aimed at investigating whether doxycycline hydrochloride (DCH), an inhibitor of MMPs, could reverse EMT in MRTK to exert an antitumour effect by regulating MMPs and the cytoskeleton. Methods. The existence of EMT in MRTK cells was verified by bioinformatics analysis, immunofluorescence, and western blotting (WB). In vitro, the proliferation, migration, and invasion abilities of G401 cells were examined by Cell Counting Kit-8 (CCK-8), scratch, and Transwell assays, respectively. The effect of DCH on tumour growth in tumour-bearing mice was explored in in vivo experiments, and the expression of MMP2 and MMP9 and EMT correlation indexes was measured by immunofluorescence and WB, and the changes in cytoskeletal F-actin and beta-tubulin were measured by fluorescence. Results. The altered extracellular matrix (ECM) composition, EMT, and high expression of MMP2 and MMP9 existed in MRTK. DCH inhibited the proliferation, migration, and invasion of G401 cells in vitro. In vivo, DCH inhibited tumour growth in mice, downregulated the expression of MMP2 and MMP9, and partially reversed EMT. Alternatively, DCH resulted in cytoskeletal rearrangements of G401 cells. Conclusions. DCH, as an MMP inhibitor, is used for the first time in MRTK research, showing good antitumour effects by reversing EMT and potentially providing new therapeutic measures for MRTK treatment."
基金机构：Chongqing Talent Program "lump sum project" [Cstc2019jscx-tjsbX0003]; Special Key Project of Chongqing Technology Innovation and Application Development [2020-SW (Reserve)-112]; Kunming City Health Science and Technology Talent "1000" training Project [2020-0201-001]; Kunming Health and Health Commission Health Research Project [202001AY070001-271]; Kunming Medical Joint Project of Yunnan Science and Technology Department [2022-ETYY-YJ-03]; open research fund of Children's Health and Disease Clinical Medical Research Center of Yunnan Province; [cstc2021ycjh-bgzxm0253]
基金资助正文："This study was supported by the Chongqing Talent Program ""lump sum project"" (No. cstc2021ycjh-bgzxm0253), the Special Key Project of Chongqing Technology Innovation and Application Development (No. Cstc2019jscx-tjsbX0003), the Kunming City Health Science and Technology Talent ""1000"" training Project (No. 2020-SW (Reserve)-112), the Kunming Health and Health Commission Health Research Project (No. 2020-0201-001), and the Kunming Medical Joint Project of Yunnan Science and Technology Department (No. 202001AY070001-271) and the open research fund of Children's Health and Disease Clinical Medical Research Center of Yunnan Province (No. 2022-ETYY-YJ-03)."
