ERK5抑制剂XMD17-109通过下调ITPRIP表达抑制胶质瘤进展  

ERK5 inhibitor XMD17-109 inhibits glioma progression by down-regulating ITPRIP expression

作　　者：王昕雯 曹长春 朱亮 杜宇 孙增先 WANG Xinwen;CAO Changchun;ZHU Liang;DU Yu;SUN Zengxian(Department of Pharmacy,Lianyungang Hospital Affiliated to Xuzhou Medical University,Lianyungang,Jiangsu 222061,China;Department of Pharmacy,Huai’an Clinical College of Xuzhou Medical University,Huai’an,Jiangsu 223300,China;Department of Pharmacy,the Affiliated Huai’an NO.1 People’s Hospital of Nanjing Medical University,Huai’an,Jiangsu 223300,China)

机构地区：[1]徐州医科大学附属连云港医院药学部,江苏连云港222061 [2]徐州医科大学淮安临床学院药学部,江苏淮安223300 [3]南京医科大学附属淮安第一医院药学部,江苏淮安223300

出　　处：《重庆医学》2023年第23期3546-3553,共8页Chongqing medicine

基　　金：中国博士后科学基金项目(2021M701487)。

摘　　要：目的基于细胞外信号调节激酶5(ERK5)/肌醇1,4,5-三磷酸受体相互作用蛋白(ITPRIP)信号通路研究XMD17-109对胶质瘤细胞活力的影响及其分子机制。方法常规培养胶质瘤细胞U251,通过XMD17-109抑制ERK5活性,转染RNA片段和质粒分别构建ERK5敲低和ERK5过表达模型。实验分为XMD17-109组、Control组、siERK5组、siNC组、ERK5-OE组、Vector组、ERK5-OE+XMD17-109组和Vector+XMD17-109组。分别采用CCK-8、划痕、流式细胞术等实验检测细胞活力,逆转录实时荧光定量PCR(RT-qPCR)和Western blot检测ERK5和ITPRIP的mRNA和蛋白表达水平。结果XMD17-109组相较于Control组细胞活力下降,ITPRIP表达水平降低(P<0.05);siERK5组相较于siNC组细胞活力下降,ITPRIP表达水平降低(P<0.05);ERK5-OE组相较于Vector组细胞活力增强,ITPRIP表达水平上升(P<0.05);ERK5-OE+XMD17-109组相较于Vector+XMD17-109组细胞活力增强,ITPRIP表达水平上升(P<0.05)。结论XMD17-109通过抑制ERK5/ITPRIP信号通路抑制胶质瘤细胞的活力。Objective To investigate the effect of XMD17-109 on the viability of glioma cells and its molecular mechanism based on extracellular signal-regulated kinase 5(ERK5)/inositol 1,4,5-trisphosphate receptor-interacting protein(ITPRIP)signaling pathway.Methods U251 glioma cells were routinely cultured,and ERK5 activity was inhibited by XMD17-109.ERK5 knockdown and ERK5 overexpression models were constructed by transfection of RNA fragments and plasmids,respectively.Cells were divided divided into the XMD17-109 group,the Control group,the siERK5 group,the siNC group,siERK5-OE group,the Vector group,the ERK5-OE+XMD17-109 group and the Vector+XMD17-109 group.The cell viability was detected by CCK-8,scratch and flow cytometry experiments and so on.The mRNA and protein expression levels of ERK5 and ITPRIP were detected by reverse transcription-quantitative real time PCR(RT-qPCR)and Western blot.Results Compared with the Control group,the cell viability of the XMD17-109 group decreased,and the expression level of ITPRIP decreased(P<0.05).Compared with the siNC group,the cell viability of the siERK5 group was decreased,and the expression level of ITPRIP was decreased(P<0.05).Compared with the Vector group,the cell viability of the ERK5-OE group was enhanced,and the expression level of ITPRIP was increased(P<0.05).Compared the with Vector+XMD17-109 group,t he cell viability of the ERK5-OE+XMD17-109 group was enhanced,and the expression level of ITPRIP was increased(P<0.05).Conclusion XMD17-109 can inhibit the viability of glioma cells by inhibiting ERK5/ITPRIP signaling pathway,which is expected to be a potential drug for glioma treatment.

关 键 词：细胞外信号调节激酶5 肌醇1 4 5-三磷酸受体相互作用蛋白 XMD17-109 胶质瘤 抑制剂 

分 类 号：R739.41[医药卫生—肿瘤]