兰州大学机构库 >学院待认领
HDAC抑制剂MGCD0103联合吉西他滨对人骨肉瘤MG-63细胞抑制作用的实验研究
Alternative TitleExperimental Study of MGCD0103 and gemcitabine inhibit of Human osteosarcoma MG-63 cells in vitro
胡旭昌
Thesis Advisor王栓科
2013-05-20
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name硕士
Keyword组蛋白去乙酰化酶抑制剂 骨肉瘤 MG-63细胞 MGCD0103 吉西他滨
Abstract   目的:研究新型的组蛋白去乙酰化酶(histone deacetylase,HDAC)抑制剂(简称HDACI)MGCD0103对人骨肉瘤细胞株MG-63的增殖抑制和诱导凋亡的作用,并探讨其可能的作用机制。    方法:将不同浓度的MGCD0103(0.01、0.1、1、10、100umol/L)分别作用于MG-63细胞,MTT比色法检测不同浓度梯度的 MGCD0103 干预MG-63细胞24h和48h后细胞的生长抑制率,同时设置对照组和空白组,并绘制浓度、抑制率曲线图形。相差显微镜和荧光显微镜下观察MGCD0103作用MG-63 细胞凋亡的情况。实时定量PCR检测处理后MG-63细胞HDAC3、MTA1mRNA表达的变化,Western Blotting检测Bax、VEGF表达水平的改变。    结果:MGCD0103能显著的抑制人骨肉瘤细胞的增殖,且抑制率表现出剂量和时间依赖的关系。MGCD0103作用于MG-63 细胞后,大量具有凋亡形态特征的细胞出现,凋亡比例明显增高,组蛋白的乙酰化水平显著提高,HDAC3、MTA1、VEGF及Bax的表达被分别下调。    结论:MGCD0103通过诱导细胞凋亡及抑制细胞增殖而发挥体外的抗骨肉瘤作用,其作用机制涉及组蛋白乙酰化水平以及细胞周期和凋亡相关基因表达的调控。HDAC抑制剂作为一类新的抗肿瘤药物,有希望应用于骨肉瘤治疗。
Other Abstract   Objective:To investigate the effect of novel histone deacetylase inhibitors(HDACI) MGCD0103,on proliferation and apoptosis of human osteosarcoma cell lines MG-63 in vitro,and explore the mechanism involved.    Methods:Cultured MG-63 cells were exposed to different concentrations of MGCD0103 (0.01、0.1、1、10、100umol/L) for different durations.MG-63 were treated with different concentration of MGCD0103 for 24 hours,48 hours,then cell proliferation inhibition were measured by MTT colorimetric assay,inhibition rate curve and time inhibition rate curve.The cell apoptosis was qualitatively detected by Phase Contrast Microscope、Fluorescence microscope respectively .The mRNA expression ofHDAC3、MTA1、after MGCD0103 treatment Was measured by real-time RT-PCR.Western Blotting Was used to detect the expressions of Bax and VEGF.    Results:MGCD0103 could inhibit the growth of human osteosarcoma cell lines obviously,in a time and dose dependent manner.After MG-63 cells were treatcd with MGCD0103,apoptotic cells of typical morphological changes appeared,apoptotic ratio Was increased considerably,acetyl level of histone Was promoted significantly,and expressions of HDAC3、MTA1、VEGF and Bax were up regulated or down-regulated respectively.    Conclusion:MGCD0103 has antitumor effect on osteosarcoma in vitro through inducing cell apoptosis and inhibiting cell proliferation,which might be related to theregulation of acetyl level of histone and expression of genes involved.MGCD0103 is promising to be used as anew antitumor drug to treat osteosarcoma.
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Language中文
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/224110
Collection学院待认领
Affiliation临床医学院
Recommended Citation
GB/T 7714
胡旭昌. HDAC抑制剂MGCD0103联合吉西他滨对人骨肉瘤MG-63细胞抑制作用的实验研究[D]. 兰州. 兰州大学,2013.
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