酪氨酸激酶RON在霍奇金淋巴瘤中的表达及其对细胞增殖的影响

Expression of tyrosine kinase RON in Hodgkin's lymphoma and its effect on cell proliferation and apoptosis

目的探讨RON在霍奇金淋巴瘤(HL)中的表达及其对HL细胞增殖的影响。方法采用免疫组化法检测RON蛋白在HL中的表达情况,并用原位杂交法检查RON的表达与EB病毒感染的相关性。将HL细胞株(L428细胞)分成4组:空白对照组、Zt/f2(2F2)预处理组、巨噬细胞刺激蛋白(MSP)刺激组和联合处理组。通过四唑盐比色法、流式细胞术分别检测L428细胞的增殖和凋亡。结果 RON蛋白在HL呈异常高表达(47.86%),其表达率与EB病毒感染呈正相关(r=0.32,P=0.02)。与空白对照组相比,MSP刺激组RON的磷酸化被激活,L428细胞增殖明显,Zt/f2(2F2)预处理组与联合治疗组细胞增殖则受抑制(P均<0.05)。同时,Zt/f2(2F2)组L428细胞凋亡被诱导,且呈时间依赖性。结论 RON的表达促进HL瘤细胞增殖,而抑制RON表达可诱导其凋亡。

Objective To investigate the expression of RON in Hodgkin＇s lymphoma （HL） and its effect on cell proliferation and apoptosis. Methods The expression of RON protein in HL was detected by immunohistochemistry, and the relationship between expression of RON protein and EB virus infection by in situ Hybridization. HL cell lines （L428 cells） were divided into 4 groups： blank control group, Zt/f2 （2F2） pretreatment group, MSP stimulation group and combined treatment group. The proliferation and apoptosis of L428 cells in all the groups were detected by MTT method and flow cytometry, respectively. Results The RON protein overexpressed in HL （47.86%）, and the expression rate was significantly correlated with EB virus infection （r = 0.32, P = 0.02）. In the MSP stimulation group, the RON phosphorylation were activated and the proliferation of L428 cells were obviously increased, while in the Zt/f2 （2F2） pretreatment group and the combined treatment group, the proliferation were remarkably inhibited, when compared with the blank control group （all P〈 0.05）. Meanwhile, in the Zt/f2 （2F2） pretreatment group, the apoptosis of L428 cells were induced in a time dependent manner. Conclusion Expression of RON promotes the proliferation of HL cell lines, and the inhibition of RON can induce apoptosis.