RNA去甲基化酶FTO抑制剂对胶质母细胞瘤干细胞功能的影响  

Effects of RNA demethylase FTO inhibitor on function of glioblastoma stem cells

作　　者：吴润秋 田聪 张旭 于如同 WU Run-qiu;TIAN Cong;ZHANG Xu;YU Ru-tong(The First Clinical College,Xuzhou Medical University,Xuzhou Jiangsu 221002,China;Dept of Neurosurgery,The Affiliated Hospital of Xuzhou Medical University,Xuzhou Jiangsu 221002,China)

机构地区：[1]徐州医科大学第一临床学院,江苏徐州221002 [2]徐州医科大学附属医院神经外科,江苏徐州221002

出　　处：《中国药理学通报》2023年第1期125-130,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金项目(No82072796);江苏省徐州市科技局项目(NoKC21012)。

摘　　要：目的分析m^(6)A去甲基化酶FTO的抑制剂(FB23-2)对人胶质母细胞瘤干细胞活性的影响。方法运用CCK-8法和神经球形成实验检测FB23-2和替莫唑胺对GSC的影响;体外有限稀释实验检测FB23-2对GSC自我更新的影响;EdU法检测FB23-2对GSC增殖的影响;流式细胞术检测FB23-2对GSC凋亡的影响。结果CCK-8结果显示,FB23-2能够有效抑制GSC的细胞活性,其IC_(50)分别为7.11μmol·L^(-1)和4.63μmol·L^(-1)。成球实验证明,FB23-2处理组的GSC神经球的大小和数量较对照组明显减少。体外有限稀释实验表明,FB23-2可有效抑制GSC的自我更新能力;EdU参入实验显示,与对照组相比,处理组分别降至(70.59±13.74)%和(50.33±4.53)%。流式细胞术检测处理组细胞的凋亡率分别为(12.16±1.90)%和(16.77±1.17)%。结论FTO抑制剂FB23-2可抑制GSC的生长和自我更新能力,靶向FTO可能是清除GSC的潜在策略之一。Aim To investigate the effect of m^(6)A demethylase FTO inhibitor(FB23-2)on human glioblastoma stem cell activity.Methods The effects of FB23-2 and Temozolomide on GSC were detected by CCK-8 assay and neurosphere formation assay.The effect of FB23-2 on self-renewal of GSC was detected by limited dilution assay in vitro.The effect of FB23-2 on the proliferation of GSC was detected by EdU method.The effect of FB23-2 on apoptosis of glioblastoma stem cells was detected by flow cytometry.Results CCK-8 assay showed that FB23-2 could effectively inhibit the cell viability of GSC with IC_(50)values of 7.11μmol·L^(-1)and 4.63μmol·L^(-1),respectively.The size and number of GSC neural sphere in FB23-2 treatment group were significantly reduced compared with control group.In vitro limited dilution experiment showed that FB23-2 effectively inhibited the self-renewal ability of GSC.EdU incorporation experiment showed that compared with the control group,the treatment group decreased to(70.59±13.74)%and(50.33±4.53)%,respectively.The apoptotic rates of the treated group were(12.16±1.90)%and(16.77±1.17)%by flow cytometry.Conclusions FTO inhibitor FB23-2 can effectively inhibit GSC growth,self-renewal and the formation of neural sphere.In addition,FB23-2 can inhibit the proliferation of GSC and induce its apoptosis.

关 键 词：FTO FB23-2 胶质母细胞瘤干细胞 自我更新 神经球 凋亡 

分 类 号：R322.8[医药卫生—人体解剖和组织胚胎学] R329.25[医药卫生—基础医学] R342.2R730.264R739.41