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作 者:洪铁艳[1] 陈宝安[1,2] 高冲[1,2] 夏国华[2] 丁家华[1] 邵泽叶 孙耘玉[1,2] 王骏[1,2] 程坚[1] 宋慧慧[1] 薛萌[2] 鲍文[1] 赵刚[1] 肖伟 王振中
机构地区:[1]东南大学附属中大医院血液科 [2]东南大学骨髓增生异常综合征研究所,江苏南京210009 [3]连云港康缘制药有限公司,江苏连云港222001
出 处:《中国实验血液学杂志》2009年第2期373-376,共4页Journal of Experimental Hematology
基 金:国家自然科学基金资助项目,编号30070318
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。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, 0.8μg/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. 8μg/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.
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