CAL-101对BL细胞系Raji和DLBCL细胞系SUDHL-10的增殖抑制作用及其机制

Inhibitory effect and mechanism of CAL-101 on proliferation of Raji on BL Cell Line and SUDHL-10 on DLBCL cell line

目的分析不同浓度CAL-101对Burkitt淋巴瘤(BL)细胞系Raji和弥漫大B细胞淋巴瘤(DLBCL)细胞系SUDHL-10增殖的抑制作用及其相关机制。方法通过不同浓度(5μmol/L、10μmol/L、15μmol/L、20μmol/L)的CAL-101对BL细胞系Raji和DLBCL细胞系SUDHL-10进行处理,采用MTT法测定CAL-101对上述淋巴瘤细胞系增殖的抑制作用,用流式细胞术对淋巴瘤细胞凋亡情况进行测定,通过迁移实验测定CAL-101淋巴瘤细胞迁移情况的影响,并通过Western blot法对CAL-101处理后淋巴瘤细胞表达磷酸化ERK的变化进行检测。结果在CAL-101浓度≥5μmol/L时,对DLBCL细胞系SUDHL-10和BL细胞系Raji增殖具有良好的抑制作用,随着CAL-101浓度的升高,两种淋巴瘤细胞系的增殖抑制率亦明显升高(P<0.01),具有浓度依赖性的特点。随着CAL-101浓度的升高,两种淋巴瘤细胞系的细胞凋亡率亦明显升高(P<0.01),具有浓度依赖性的特点。随着CAL-101浓度的升高,CAL-101对两种淋巴瘤细胞系的细胞迁移率亦明显降低(P<0.01),具有浓度依赖性的特点。Western blot法分析结果显示,经CAL-101处理淋巴瘤细胞后,可明显降低磷酸化ERK的表达水平。结论CAL-101能够明显阻滞BL细胞系Raji和DLBCL细胞系SUDHL-10增殖,促使细胞凋亡,阻滞细胞迁移至淋巴瘤基底细胞,其发生机制可能与ERK信号途径阻断密切相关。

Objective To analyze the inhibitory effect and related mechanism of different concentrations of CAL-101 on proliferation of Burkitt lymphoma(BL)cell line Raji and diffuse large B cell lymphoma(DLBCL)cell line SUDHL-10.Methods Raji of BL cell line and SUDHL-10 of DLBCL cell line were treated by different concentration of CAL-101,inhibition effect of CAL-101 on the proliferation of the lymphoma cell lines was determined by MTT method;the apoptosis of lymphoma cells was determined by flow cytometry;the effect of CAL-101 on the migration of lymphoma cells was detected by migration experiment and the expression of phosphorylated ERK on lymphoma cells treated with CAL-101 was detected by Western blot method.Results The CAL-101 showed significant inhibitory effect on the proliferation of SUDHL-10 in DLBCL cell line and Raji in BL cell line when the concentration was≥5 mol/L;with the increase of CAL-101 concentration,the inhibition rate of the two kinds of lymphoma cell lines proliferation increased significantly(P<0.01)in a concentration dependent manner.Also with the increase of CAL-101 concentration,the apoptosis rate of the two kinds of lymphoma cell lines increased significantly(P<0.01)in a concentration dependent manner.With the increase of CAL-101 concentration,the cell migration rate of the two kinds of lymphoma cell lines also decreased significantly(P<0.01)in a concentration dependent manner.The results of Western blot analysis showed that the expression of phosphorylated ERK on lymphoma cells treated with CAL-101 was significantly reduced.Conclusion CAL-101 can significantly block the proliferation of Raji in BL cell line and SUDHL-10 in DLBCL cell line,promote cell apoptosis,hinder cell migration to lymphoma basal cells,and the mechanism may be closely related to the block of ERK signaling pathway.