"TRAIL and Celastrol Combinational Treatment Suppresses Proliferation, Migration, and Invasion of Human Glioblastoma Cells via Targeting Wnt/β-catenin Signaling Pathway"

作者全名："Qin, Jing-jing; Niu, Meng-da; Cha, Zhe; Geng, Qing-hua; Li, Yu-lin; Ren, Chun-guang; Molloy, David P.; Yu, Hua-rong"

作者地址："[Qin, Jing-jing; Niu, Meng-da; Cha, Zhe; Geng, Qing-hua; Li, Yu-lin; Yu, Hua-rong] Chongqing Med Univ, Res Ctr Neurosci, Chongqing 400016, Peoples R China; [Ren, Chun-guang] Chongqing Med Univ, Sch Basic Med Sci, Dept Cell Biol & Genet, Lab Dev Biol, Chongqing 400016, Peoples R China; [Molloy, David P.] Chongqing Med Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Chongqing 400016, Peoples R China"

通信作者："Yu, HR (通讯作者)，Chongqing Med Univ, Res Ctr Neurosci, Chongqing 400016, Peoples R China."

来源：CHINESE JOURNAL OF INTEGRATIVE MEDICINE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001091031300001

JCR分区：Q2

影响因子：2.2

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：celastrol; Chinese medicine; tumor necrosis factor-related apoptosis-induced ligand; glioblastoma; beta-catenin; Tripterygium wilfordii

摘要："Objective: To investigate the mechanistic basis for the anti-proliferation and anti-invasion effect of tumor necrosis factor-related apoptosis-induced ligand (TRAIL) and celastrol combination treatment (TCCT) in glioblastoma cells. Methods: Cell counting kit-8 was used to detect the effects of different concentrations of celastrol (0-16 mu mol/L) and TRAIL (0-500 ng/mL) on the cell viability of glioblastoma cells. U87 cells were randomly divided into 4 groups, namely control, TRAIL (TRAIL 100 ng/mL), Cel (celastrol 0.5 mu mol/L) and TCCT (TRAIL 100 ng/mL+ celastrol 0.5 mu mol/L). Cell proliferation, migration, and invasion were detected by colony formation, wound healing, and Transwell assays, respectively. Quantitative reverse transcription polymerase chain reaction and Western blotting were performed to assess the levels of epithelial-mesenchymal transition (EMT) markers (zona occludens, N-cadherin, vimentin, zinc finger E-box-binding homeobox, Slug, and beta-catenin). Wnt pathway was activated by lithium chloride (LiCl, 20 mol/L) and the mechanism for action of TCCT was explored. Results: Celastrol and TRAIL synergistically inhibited the proliferation, migration, invasion, and EMT of U87 cells (P<0.01). TCCT up-regulated the expression of GSK-3 beta and down-regulated the expression of beta-catenin and its associated proteins (P<0.05 or P<0.01), including c-Myc, Cyclin-D1, and matrix metalloproteinase (MMP)-2. In addition, LiCl, an activator of the Wnt signaling pathway, restored the inhibitory effects of TCCT on the expression of beta-catenin and its downstream genes, as well as the migration and invasion of glioblastoma cells (P<0.05 or P<0.01). Conclusions: Celastrol and TRAIL can synergistically suppress glioblastoma cell migration, invasion, and EMT, potentially through inhibition of Wnt/beta-catenin pathway. This underlies a novel mechanism of action for TCCT as an effective therapy for glioblastoma."

基金机构："Scientifi c and Technological Research Programme of Chongqing Municipal Education Commission, China [KJ130320]"

基金资助正文："Supported by Scientifi c and Technological Research Programme of Chongqing Municipal Education Commission, China (No. KJ130320)"