地高辛对人B细胞淋巴瘤细胞增殖、凋亡的影响及其分子机制的研究  

Effects of digoxin on proliferation and apoptosis in human B cell lymphoma cell lines and its' mechanism

作　　者：张文婷[1] 江莲[1] 朱秀丽[1] 刘翠萍[1] 陈健[1] ZHANG Wenting, JIANG Lian,ZHU Xiuli,LIU Cuiping, CHEN Jian(Department ol Paediatrics, the Fourth Hospital ol Hebei Medical University, Shijiazhuang Hebei 050011, Chin)

机构地区：[1]河北医科大学第四医院儿科,河北石家庄050011

出　　处：《转化医学杂志》2018年第2期74-78,共5页Translational Medicine Journal

基　　金：河北省科技计划项目(13277799D)

摘　　要：目的通过观察强心甾类药物地高辛对人B细胞淋巴瘤Raji细胞增殖和凋亡的影响,研究其可能的分子机制。方法体外培养Raji细胞,实验组细胞培养基中加入二甲基亚砜溶解的地高辛,分别以不同浓度地高辛对其进行干预;对照组细胞培养基中加入与实验组等体积的二甲基亚砜。通过四甲基偶氮唑蓝法检测细胞增殖的变化,流式细胞术检测其对细胞周期的影响及细胞凋亡情况,反转录聚合酶链式反应(RTPCR)分析细胞内Survivin、Caspase-3 mRNA的变化。结果地高辛体外对Raji细胞增殖具有明显的抑制作用(P<0.05),在一定范围内与时间、剂量呈依赖关系。实验组地高辛作用于Raji细胞48 h后,与对照组相比,G0/G1期细胞数减少,G2/M期细胞数增加,差异具有统计学意义(P<0.05)。实验组出现明显的凋亡峰,对照组未见凋亡峰,或仅有低平的凋亡峰。与对照组相比,Raji细胞中Survivin mRNA的表达减少,Caspase-3mRNA的表达增加(P<0.05),并与剂量呈依赖关系。结论地高辛对Raji细胞具有抑制增殖及诱导凋亡的作用,通过阻滞细胞于G2/M期,抑制Raji细胞的增殖,通过下调Survivin的表达进而激活Caspase-3诱导其凋亡,此可能为地高辛抗肿瘤作用的机制之一。ObjectiveTo investigate the proliferation and apoptotic effect of digoxin from cardiac glycosides in lymphoma cell line Raji and explore the possible molecular mechanism. MethodsRaji cells were cultivated in vitro. The experimental groups were treated with different concentration of digoxin, and the control group was treated with the same volume of dimethyl sulfoxide. Cell proliferation rate was observed by MTT assay. Cell cycle distribution and apoptotic rate were tested by flow cytometry. Expression of survivin mRNA and Caspase-3 mRNA in Raji cells were measured by reverse transcription polymerase chain reaction. ResultsThe proliferation of Raji cells was inhibited by digoxin in vitro with concentration and time dependence. After treated with digoxin for 48 h,the cell numbers in G2/M phase of experimental groups were more than those of the control group. Cell cycle distribution in experimental groups existed a significant difference （P〈0.05）. Apoptotic peak emerged obviously in experimental groups. There was no or only low apoptotic peak in control group. Compared with control group,the expression of Survivin mRNA of experimental groups was decreased and the expression of Caspase-3 mRNA was increased （P〈0.05）. ConclusionDigoxin has the effect of inhibiting proliferation and inducing apoptosis of Raji cells. Digoxin induced cell cycle arrest in G2/M phase to inhibit the growth of Raji, and downregulation of survivin expression of activation of Caspase-3 expression, which may be a possible anticancer mechanism.

关 键 词：地高辛 B细胞淋巴瘤 细胞周期 生存素 CASPASE-3 

分 类 号：R394.6[医药卫生—医学遗传学]