Abstract:

Objective　To study the effect of digoxin on the invasion ability of non-hodgkin lymphoma（NHL） raji cells，and to preliminarily investigate its mechanism of action. Methods　The 30 tissue samplec of non-Hodgkin lymphoma were taken in the Pathological Department of the Fourth Hospital of Hebei Medical University from Oct. 2010 to Dec. 2013. （1） The protein expression of Tiam-1 and Rac-1 in NHL were detected by immunohistochemical S-P method. （2）With different concentration of digoxin，the changes in expression levels of Tiam-1 and Rac-1 within raji cells were detected via cell invasion test and qRT-PCR. Results　（1）Immunohistochemical result indicated：the positive rates of protein Tiam-1（70%） and Rac-1（73.33%） in NHL were higher than those in normal lymph node tissues with statistical significance（P＜0.05）. Correlation analysis indicated there was correlation between Tiam-1 and Rac-1，with a correlation coefficient of r＝0.757（P＜0.01）. （2）Cell invasion test indicated：after 48 h treatment by digoxin of different concentrations，the invasion rate reduced with the increasing digoxin concentration，and the results were statistically significant（P＜0.01）. （3）qRT-PCR result indicated：after 48 h treatment by digoxin of different concentrations，statistical difference was observed in the relative expression levels of Tiam-1 and Rac-1 between groups；the relative expression levels reduced with the increasing digoxin concentrations（P＜0.05）. Conclusion　Digoxin，a cardiac glycoside，is able to inhibit lymphoma invasion or metastasis to some extent via regulating the expressions of Tiam-1 and Rac-1.

Key words: digoxin, non-Hodgkin lymphoma, invasion, raji cell, Tiam-1, Rac-1

摘要：

目的　了解强心苷类药物地高辛对非霍奇金淋巴瘤raji细胞侵袭能力的影响，并对其作用机制进行初步探讨。方法　选取河北医科大学第四医院病理科2010年10月至2013年12月手术切除的非霍奇金淋巴瘤组织标本30例，采用免疫组化S-P方法检测非霍奇金淋巴瘤T淋巴瘤侵袭转移诱导因子1（Tiam-1）及Ras相关的C3肉毒素底物1（Rac-1）蛋白表达情况；通过细胞侵袭实验以及实时荧光定量聚合酶链式反应（PCR）技术检测不同浓度地高辛作用于raji细胞后Tiam-1、Rac-1表达水平变化。结果　免疫组化结果显示，非霍奇金淋巴瘤中Tiam-1蛋白染色阳性率（70%）及Rac-1蛋白染色阳性率（73.33%）均高于正常淋巴结组织，差异有统计学意义（P＜0.05）。相关分析结果显示，Tiam-1及Rac-1具有相关性，相关系数r＝0.757（P＜0.01）。细胞侵袭实验结果显示，不同浓度组地高辛作用raji细胞48 h后，随着作用浓度的增加侵袭率下降，差异有统计学意义（P＜0.01）。实时荧光定量PCR结果显示，不同浓度的地高辛分别作用于raji细胞48 h，各组之间Tiam-1及Rac-1的相对表达量差异有统计学意义（P＜0.05），并随着作用浓度的增加相对表达量降低。结论　强心苷类药物地高辛可通过调节Tiam-1及Rac-1因子的表达对淋巴瘤侵袭及转移起到一定抑制作用。

关键词: 地高辛, 非霍奇金淋巴瘤, 侵袭, raji细胞, Tiam-1, Rac-1