[1]靳娟娟,姚 玉.MutT同系物1抑制剂对多发性骨髓瘤细胞增殖和凋亡的影响[J].陕西医学杂志,2021,50(8):934-936,948.[doi:DOI:10.3969/j.issn.1000-7377.2021.08.008]
　JIN Juanjuan,YAO Yu.Effect of MutT homologue-1 inhibitor on proliferation and apoptosis of multiple myeloma cells[J].,2021,50(8):934-936,948.[doi:DOI:10.3969/j.issn.1000-7377.2021.08.008]
点击复制

MutT同系物1抑制剂对多发性骨髓瘤细胞增殖和凋亡的影响
分享到：

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
50
期数:
2021年8期
页码:
934-936,948
栏目:
基础研究
出版日期:
2021-08-05

文章信息/Info

Title:
Effect of MutT homologue-1 inhibitor on proliferation and apoptosis of multiple myeloma cells
作者:
靳娟娟; 姚 玉
(铜川市人民医院血液科,陕西 铜川 727100)
Author(s):
JIN Juanjuan; YAO Yu
(Department of Hematology,Tongchuan People's Hospital,Tongchuan 727100,China)
关键词:
多发性骨髓瘤;  MutT同系物1;  TH588;  细胞增殖;  细胞凋亡;  生物学特性
Keywords:
Multiple myeloma;  MTH1;  TH588;  Cell proliferation;  Apoptosis;  Biological property
分类号:
R 733.3
DOI:
DOI:10.3969/j.issn.1000-7377.2021.08.008
文献标志码:
A
摘要:
目的:探索MutT同系物1(MTH1)抑制剂对多发性骨髓瘤(MM)细胞增值和凋亡的影响。方法:用0.0、1.5、3.0、6.0、10.0 μmol/L的MTH1抑制剂TH588处理多发性骨髓瘤U266细胞,用Multiskan FC酶标仪测定各时间点每孔悬液的荧光强度,用Trizol试剂提取RNA进行反转录,Q-PCR扩增仪检测MTH1表达水平的变化情况,用Ca2+依赖的磷脂结合蛋白(Annexin V)合并碘化丙啶(PI)染色法共同捕获凋亡细胞,并用流式细胞仪测定细胞凋亡。结果:不同浓度MTH1抑制剂TH588处理U266细胞后培养72 h,测定不同时间点混悬液的荧光强度和细胞中MTH1的表达水平。其中经TH588处理组的荧光强度与0.0 μmol/L浓度组相比显著降低,且MTH1的表达水平也显著低于0.0 μmol/L浓度组,随着TH588的浓度升高,MTH1表达水平呈明显降低趋势,差异均具有统计学意义(均P<0.05); 细胞凋亡实验结果表明,不同浓度MTH1抑制剂TH588处理U266细胞后,经TH588处理组与0.0 μmol/L浓度组相比,APC和PI双阴性细胞的比例有显著下降,且浓度越高下降越明显,差异均具有统计学意义(均P<0.05)。结论:MTH1抑制剂TH588能显著抑制细胞增殖、促进细胞凋亡,且表现出明显的剂量依赖性,此为临床开发治疗多发性骨髓瘤的新靶点、新药物提供了实验依据。
Abstract:
Objective:To explore the effect of MutT homolog 1(MTH1)inhibitor on the proliferation and apoptosis of multiple myeloma(MM)cells.Methods:MM U266 cells were treated with 0.0,1.5,3.0,6.0,10.0 μmol/L MTH1 inhibitor TH588.The fluorescence intensity of each well suspension at each time point was measured by multiskan FC microplate.The RNA was extracted by Trizol reagent for reverse transcription.The expression of MTHl was detected by Q-PCR.The apoptotic cells were captured by Ca2+ dependent phospholipid binding protein(Annexin V)and propidium iodide(PI)staining.The apoptosis was detected by flow cytometry.Results:U266 cells were treated with different concentrations of TH588 and cultured for 72 hours.The fluorescence intensity of the well suspension and the expression level of MTH1 in the cells were measured at different time points.Among them,the fluorescence intensity of the TH588-treated group was significantly lower than that of the 0.0 μmol/L concentration group,and the expression level of MTH1 was also significantly lower than that of the 0.0 μmol/L concentration group,and as the concentration of TH588 increased,the expression level of MTH1 was significantly reduced(all P<0.05).The apoptosis experiment results showed that after treated with different concentrations of TH588,the proportion of APC and PI double negative cells decreased significantly in comparison with the control group,and the higher the concentration,the more obvious the decrease(all P<0.05).Conclusion:The MTH1 inhibitor TH588 can significantly inhibit cell proliferation and promote cell apoptosis,and shows an obvious dose-dependence,which provides experimental basis for the clinical development of new targets and new drugs for the treatment of multiple myeloma.

参考文献/References:

[1] Patel A,Burton D,Halvorsen K,et al.MutT Homolog 1(MTH1)maintains multiple KRAS-driven pro-malignant pathways[J].Oncogene,2015,34(20):2586-2596.
[2] 邢 玉.益肾强骨扶正法联合化疗治疗多发性骨髓瘤临床研究[J].陕西中医,2018,39(7):935-937,946.
[3] Saleh A,Gokturk C,Warpman-Berglund U,et al.Development and validation of method for TH588 and TH287,potent MTH1 inhibitors and new anti-cancer agents,for pharmacokinetic studies in mice plasma[J].Journal of Pharmaceutical and Biomedical Analysis,2015,104(2):1-11.
[4] 谭 奎,沈婵娟,张 玲,等.多发性骨髓瘤患者骨髓CD269和CD317基因的差异性表达研究[J].现代检验医学杂志,2017,32(6):64-66.
[5] Wang HP,Meng HT,Wang JH,et al.Clinical characteristics and prognostic values of 1p32.3 deletion detected through fluorescence in situ hybridization in patients with newly diagnosed multiple myeloma:A single-center study in China[J].Frontiers of Medicine,2020,14(3):327-334.
[6] Zhou G,Meng XY,Liu SQ.Association between diabetes mellitus,hypertension,hyperlipidemia,chronic viral hepatitis,and the risk of multiple myeloma:A case-control study[J].Oncology and Translational Medicine,2020,6(2):45-50.
[7] Kumar A,Kawamura T,Kawatani M,et al.Identification and structure-activity relationship of purine derivatives as novel MTH1 inhibitors[J].Chemical Biology and Drug Design,2017,89(6):862-869.
[8] 刘海英.中医辨证论治配合化疗治疗多发性骨髓瘤肾病及对患者生存质量的影响[J].陕西中医,2015,36(4):407-408.
[9] Chen Y,Fu WJ,Xu LP,et al.Comparison of outcomes after human leukocyte antigen-matched and haploidentical hematopoietic stem-cell transplantation for multiple myeloma[J].Chinese Medical Journal,2019,132(15):1765-1772.
[10] Fotouhi A,Cornella N,Ramezani M,et al.Investigation of micronucleus induction in MTH1 knockdown cells exposed to UVA,UVB or UVC[J].Mutation Research Genetic Toxicology and Environmental Mutagenesis,2015,793(4):161-165.
[11] 王 欣,吴 颖,张 林,等.靶向MTH1抑制多发性骨髓瘤细胞增殖和诱导凋亡的作用研究[J].中国实验血液学杂志,2020,28(5):1598-1604.
[12] Cheng Q,Xin LI,Wang Y,et al.The ceramide pathway is involved in the survival,apoptosis and exosome functions of human multiple myeloma cells in vitro[J].Acta Pharmacologica Sinica,2018,39(4):561-568.
[13] Jin J,Cheng S,Wang Y,et al.SRC3 expressed in bone marrow mesenchymal stem cells promotes the development of multiple myeloma[J].Acta Biochimica et Biophysica Sinica,2019,51(12):1258-1266.
[14] 宋 玉,胡 轶.MTH1在非小细胞肺癌中的表达及其与预后的关系[J].临床与病理杂志,2019,39(3):523-528.
[15] 张东伟,孔晋亮,蓝 冰,等.非小细胞肺癌患者病理组织中MTH1的表达和临床意义的研究[J].国际呼吸杂志,2019,39(18):1366-1372.
[16] Cao W,Gao WH,Sun YH,et al.AUNP flares-capped mesoporous silica nanoplatform for MTH1 detection and inhibition[J].Biomaterials,2015,69:212-221.
[17] Satomi F,Yasumasa O,Shinya A,et al.Mth1 deficiency provides longer survival upon intraperitoneal crocidolite injection in female mice[J].Free Radical Research,2020,54(2):195-205.
[18] Petrocchi A,Leo E,Reyna NJ,et al.Identification of potent and selective MTH1 inhibitors[J].Bioorganic and Medicinal Chemistry Letters,2016,26(6):1503-1507.
[19] 吴晓波,曹亚丽,魏文嵩.凋亡抑制蛋白生存素在乳腺癌中的表达及其意义:临床标本47例分析[J].中国急救复苏与灾害医学杂志,2008,3(12):722-724.
[20] Stewart JJ.A method for predicting individual residue contributions to enzyme specificity and binding-site energies,and its application to MTH1[J].Journal of Molecular Modeling,2016,22(11):259-259.

相似文献/References:

[1]朱清红,李德奎,罗 英.血清尿酸、β2微球蛋白和尿液轻链联合检测〖JZ〗在多发性骨髓瘤早期诊断中的应用[J].陕西医学杂志,2019,(9):1235.
　ZHU Qinghong,LI Dekui,LUO Ying..Combined detection of serum uric acid，β2 microglobulin and urine light chain〖JZ〗in early diagnosis of multiple myeloma[J].,2019,(8):1235.
[2]杜娟英,薛海鲸.多发性骨髓瘤患者血清微小RNA-424、可溶性晚期糖基化终末产物受体、c-kit受体蛋白检测及临床意义[J].陕西医学杂志,2022,51(12):1585.[doi:DOI:10.3969/j.issn.1000-7377.2022.12.028]
　DU Juanying,XUE Haijing.Detection and clinical significance of serum miR-424,sRAGE and CD117 in patients with multiple myeloma[J].,2022,51(8):1585.[doi:DOI:10.3969/j.issn.1000-7377.2022.12.028]
[3]张治业,余醒醒,张 璐,等.CD166对多发性骨髓瘤RPMI-8226细胞增殖、凋亡及自噬的影响实验研究[J].陕西医学杂志,2023,52(12):1675.[doi:DOI:10.3969/j.issn.1000-7377.2023.12.010]
　ZHANG Zhiye,YU Xingxing,ZHANG Lu,et al.Effects of CD166 on proliferation,apoptosis and autophagy of multiple myeloma RPMI-8226 cells[J].,2023,52(8):1675.[doi:DOI:10.3969/j.issn.1000-7377.2023.12.010]
[4]刘虹伶,王美佳,晏青霞.多发性骨髓瘤患者血清β2-微球蛋白、肿瘤坏死因子-α、乳酸脱氢酶检测及临床意义[J].陕西医学杂志,2024,(3):399.[doi:DOI:10.3969/j.issn.1000-7377.2024.03.024]
　LIU Hongling,WANG Meijia,YAN Qingxia.Detection and clinical significance of serum β2-microglobulin,tumor necrosis factor-α and lactate dehydrogenase in patients with multiple myeloma[J].,2024,(8):399.[doi:DOI:10.3969/j.issn.1000-7377.2024.03.024]
[5]滕 远,李莉娟,张连生.髓细胞白血病1抑制剂在多发性骨髓瘤治疗中的研究进展[J].陕西医学杂志,2024,(6):858.[doi:DOI:10.3969/j.issn.1000-7377.2024.06.029]
　TENG Yuan,LI Lijuan,ZHANG Liansheng.Research progress of myeloid cell leukemia 1 inhibitors in treatment of multiple myeloma[J].,2024,(8):858.[doi:DOI:10.3969/j.issn.1000-7377.2024.06.029]
[6]赵思捷,余 航,党珮珠,等.多发性骨髓瘤患者合并心包积液危险因素分析及列线图预测模型构建[J].陕西医学杂志,2024,(12):1635.[doi:DOI:10.3969/j.issn.1000-7377.2024.12.009]
　ZHAO Sijie,YU Hang,DANG Peizhu,et al.Risk factors of multiple myeloma patients with pericardial effusion and construction of nomogram prediction model[J].,2024,(8):1635.[doi:DOI:10.3969/j.issn.1000-7377.2024.12.009]

备注/Memo

备注/Memo:
基金项目:陕西省卫生健康委员会科研基金资助项目(2018C008)
更新日期/Last Update: 2021-08-05