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藤黄酸对MUTZ-1细胞生长抑制作用及其机理研究

Inhibition Effect of Gambogic Acid on MUTZ-1 Cell Line and Its Possible Mechanism

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【作者】 洪铁艳陈宝安高冲夏国华丁家华邵泽叶孙耘玉王骏程坚宋慧慧薛萌鲍文赵刚肖伟王振中

【Author】 HONG Tie-Yan1,CHEN Bao-An1,2,GAO Chong1,2,XIA Guo-Hua2,DING Jia-Hua1,SHAO Ze-Ye2,SONG Yun-Yu1,2,WANG Ju1,2,CHENG Jian1,SONG Hui-Hui1,XUE Meng2,BAO Wen1,ZHAO Gang1,XAO Wei3,WANG Zhen-Zhong3 1Department of Hematology,Zhongda Hospital,Southeast University;2Institute of Myelodysplastic Syndrome,Southeast University,Nanjing 210009,Jiangsu Province,China;3Kanion Pharmaceutical Company,Lianyungang 222001,Jiangsu Province,China

【机构】 东南大学附属中大医院血液科东南大学骨髓增生异常综合征研究所连云港康缘制药有限公司

【摘要】 本研究旨在探讨藤黄酸对高危组骨髓增生异常综合征(MDS)细胞的生长抑制作用及其机制。以人MDS-RAEB细胞株MUTZ-1细胞为研究对象,采用MTT法测定增殖抑制率,流式细胞术检测细胞凋亡及细胞周期变化,用RT-PCR检测bax/bcl-2基因表达。结果表明,藤黄酸对MUTZ-1细胞有生长抑制作用,在0.2-0.8μg/ml浓度范围内随着药物浓度的增加MUTZ-1细胞的增殖抑制率增高;流式细胞学检测发现,藤黄酸浓度0、0.4、0.6、0.8μg/ml引起的MUTZ-1凋亡率分别为(5±0.5)%、(13±0.5)%、(37±0.7)%和(56±0.6)%,而且凋亡率随着药物浓度增加而增加(p<0.05)。bcl-2基因表达程度随藤黄酸剂量增加而减弱,而baxmRNA表达无明显变化。结论:藤黄酸通过诱导MUTZ-1细胞凋亡、下调bcl-2基因表达而抑制该细胞生长,这可能是藤黄酸抗肿瘤的主要机制之一。

【Abstract】 This study was aimed to investigate the effects of gambogic acid on the cells of high-risk patients with myelodysplastic syndrome(MDS)in vitro and its mechanism.The inhibition effect of gambogic acid on growth of MUTZ-1 cell line of MDS-RAEB was detected by MTT method.Apoptosis and cell cycle were detected by morphological observation and flow cytometry respectively.The expressions of bax/bcl-2 gene at mRNA level were detected by RT-PCR.The results indicated that the Gambogic acid inhibited the growth of MUTZ-1 cells,the inhibitory rate of gambogic acid with the range of 0.2-0.8 μg/ml was enhanced along with increasing of drug concentration.Flow cytometric assay showed that the apoptotic rate of MUTZ-1 cells treated by gambogic acid also was enhanced along with increasing of drug concentration,the apoptotic rates resulting from gambogic acid(0,0.4,0.6,0.8 μg/ml)were(5±0.5)%、(13±0.5)%、(37±0.7)% and(56±0.6)% respectively.The characteristic changes of apoptosis emerged in MUTZ-1 cells after being exposed to gambogic acid.Gambogic acid could significantly down-regulate the expressions of bcl-2 gene in a dose dependent manner,however,it had no effects on bax gene.It is concluded that within the range of concentration from 0.4 to 0.8 μg/ml,gambogic acid can inhibit the growth of MUTZ-1 cells by inducing their apoptosis and down-regulating the expression of bcl-2 gene,which may be one of the main mechanisms underlying its antitumor effects.

【基金】 国家自然科学基金资助项目,编号30070318
  • 【文献出处】 中国实验血液学杂志 ,Journal of Experimental Hematology , 编辑部邮箱 ,2009年02期
  • 【分类号】R285.5
  • 【被引频次】10
  • 【下载频次】255
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