[1]刘伟坤 虞荣昌 杨锐 张恒.氧化苦参碱对骨肉瘤U2OS细胞增殖的抑制作用及其机制研究[J].中国中医骨伤科杂志,2020,28(02):5-10.
 LIU Weikun YU Rongchang YANG Rui ZHANG Heng.Inhibitory Effect of Oxymatrine on the Proliferation ofOsteosarcoma U2OS Cell and Its Mechanism[J].Chinese Journal of Traditional Medical Traumatology & Orthopedics,2020,28(02):5-10.
点击复制

氧化苦参碱对骨肉瘤U2OS细胞增殖的抑制作用及其机制研究()
分享到:

《中国中医骨伤科杂志》[ISSN:1005-0205/CN:42-1340/R]

卷:
第28卷
期数:
2020年02期
页码:
5-10
栏目:
实验研究
出版日期:
2020-02-10

文章信息/Info

Title:
Inhibitory Effect of Oxymatrine on the Proliferation ofOsteosarcoma U2OS Cell and Its Mechanism
文章编号:
1005-0205(2020)02-0005-06
作者:
刘伟坤1 虞荣昌1 杨锐1 张恒1
1武汉市东西湖区人民医院骨科(武汉,430040)
Author(s):
LIU Weikun1 YU Rongchang1 YANG Rui1 ZHANG Heng1
1Department of Orthopaedics,People’s Hospital of Dongxihu District,Wuhan 430040,China.
关键词:
氧化苦参碱 骨肉瘤 细胞增殖 细胞凋亡 细胞周期
Keywords:
oxymatrine osteosarcoma cell proliferation apoptosis cell cycle
分类号:
R-33
文献标志码:
A
摘要:
目的:在分子生物学水平上探讨氧化苦参碱(Oxymatrine,OMT)对骨肉瘤U2OS细胞的生长抑制作用和潜在的作用机制。方法:体外培养骨肉瘤U2OS细胞,用不同浓度梯度的氧化苦参碱处理细胞,光学显微镜观察骨肉瘤细胞形态的变化; 四甲基偶氮唑盐(MTT)法检测不同浓度氧化苦参碱对U2OS细胞增殖的影响; Annexin Ⅴ-FITC/PI荧光双标流式细胞仪分析OMT处理后的U2OS细胞周期阻滞和凋亡的变化; RT-PCR方法分析凋亡相关分子(p53,bax,Bcl-2)mRNA的表达水平。结果:MTT法结果表明氧化苦参碱能够抑制U2OS细胞的增殖并呈剂量依赖性; 光学显微镜下观察到氧化苦参碱处理后的U2OS细胞具有凋亡特征的形态学变化; 流式细胞仪检测结果表明氧化苦参碱处理48 h后,细胞凋亡率与药物浓度呈正相关; 氧化苦参碱还能够诱导细胞周期阻滞于G0/G1期,并呈现浓度依赖性; RT-PCR检测结果表明氧化苦参碱处理后,U2OS细胞中p53 mRNA和bax mRNA的表达水平明显上升,Bcl-2 mRNA表达水平明显下降,并呈现一定的剂量依赖关系。结论:氧化苦参碱能够明显抑制骨肉瘤U2OS细胞的增殖,导致细胞周期阻滞并诱导细胞凋亡,具体分子机制可能和p53,Bcl-2,bax等凋亡调控基因相关。
Abstract:
Objective:To investigate the inhibitory effect of oxymatrine(OMT)on the growth of osteosarcoma U2OS cell and its potential mechanism.Methods:U2OS cell of osteosarcoma was cultured in vitro and treated with oxymatrine at different concentrations.The morphological change of osteosarcoma cell was observed under light microscope.The effect of oxymatrine on U2OS cell proliferation was examined by MTT assay.The flow cytometry using Annexin Ⅴ-FITC/PI staining was employed to measure the cell cycle and cell apoptosis of U2OS.RT-PCR was used to detect mRNA expression levels of p53,bax and Bcl-2.Results:MTT assay showed that oxymatrine could inhibit the proliferation of U2OS cell in a dose-dependent manner.The morphological change of apoptosis in U2OS cell treated with oxymatrine was observed under light microscope.The result of flow cytometry showed that there was a positive correlation between the apoptosis rate and the concentration of oxymatrine after 48 h treatment.Oxymatrine also induced cell cycle arrest at G0/G1 phase,and it was concentration-dependent.The result of RT-PCR showed that the expression of p53 mRNA and bax mRNA in U2OS cell increased obviously,while the expression of Bcl-2 mRNA decreased obviously,and there was a dose-dependent relationship after oxymatrine treatment.Conclusion:Oxymatrine can inhibit the proliferation of osteosarcoma U2OS cell through induction of cell cycle arrest and apoptosis.The detailed molecular mechanism may be related to p53,Bcl-2,bax and other apoptosis-regulating genes.

参考文献/References:

[1] HARRISON D J,GELLER D S,GILL J D,et al.Current and future therapeutic approaches for osteosarcoma[J].Expert Rev Anticancer Ther,2018,18(1):39-50.
[2] BIAZZO A,DE PAOLIS M.Multidisciplinary approach to osteosarcoma[J].Acta Orthop Belg,2016,82(4):690-698.
[3] LU M L,XIANG X H,XIA S H.Potential signaling pathways involved in the clinical application of oxymatrine[J].Phytother Res,2016,30(7):1104-1112.
[4] 史艳平,陈涛,李丹,等.氧化苦参碱药理作用研究进展[J].陕西医学杂志,2018,47(2):271-273.
[5] SIMPSON S,DUNNING M D,DE BROT S,et al.Comparative review of human and canine osteosarcoma:morphology,epidemiology,prognosis,treatment and genetics[J].Acta Vet Scand,2017,59(1):71-79.
[6] ZHANG Y,YANG J,ZHAO N,et al.Progress in the chemotherapeutic treatment of osteosarcoma[J].Oncol Lett,2018,16(5):6228-6237.
[7] LIAO Y H,LI C I,LIN C C,et al.Traditional Chinese medicine as adjunctive therapy improves the long-term survival of lung cancer patients[J].J Cancer Res Clin Oncol,2017,143(12):2425-2435.
[8] QI F,ZHAO L,ZHOU A,et al.The advantages of using traditional Chinese medicine as an adjunctive therapy in the whole course of cancer treatment instead of only terminal stage of cancer[J].Biosci Trends,2015,9(1):16-34.
[9] 江哲珍,祝少博,余黎,等.左旋含羞草碱诱导骨肉瘤细胞凋亡作用及机制的体外实验研究[J].生物骨科材料与临床研究,2018,15(2):1-4.
[10] LIU Y,XU Y,JI W,et al.Anti-tumor activities of matrine and oxymatrine:literature review[J].Tumour Biol,2014,35(6):5111-5119.
[11] 吴琴,高云.氧化苦参碱药理作用的分子机制研究进展[J].中国药理学通报,2015,31(6):759-762.
[12] HO J W,NGAN HON P L,CHIM W O.Effects of oxymatrine from Kushen on cancer cells[J].Anticancer Agents Med Chem,2009,9(8):823-826.
[13] 熊旋,李磊,王庆才.氧化苦参碱对肿瘤抑制作用的研究进展[J].海南医学,2018,29(8):1135-1138.
[14] 严小明,连福明,林智勤,等.苦参碱通过下调STAT3信号通路抑制骨肉瘤Saos-2细胞增殖的实验研究[J].西部医学,2015,27(9):1286-1289.
[15] 戴海龙,董成,徐玲,等.氧化苦参碱和苦参碱通过调控酪氨酸激酶-信号转导及转录激活因子信号通路对肝癌细胞SMMC-7721增殖凋亡的影响[J].中华实验外科杂志,2017,34(1):61-64.
[16] CALDWELL C C,TSCHOEP J,LENTSEH A B.Lymphocyte function during hepatic isehemia/reperfusion injury[J].J Leukoe Biol,2007,82(3):457-464.(收稿日期:2019-06-08)

备注/Memo

备注/Memo:
(收稿日期:2019-06-08)
更新日期/Last Update: 2020-02-10