二硫化二砷联合伊曲康唑对弥漫大B细胞淋巴瘤细胞增殖和凋亡的作用及Hedgehog信号通路的影响  

Effects of Arsenic Disulfide Combined with Itraconazole on Proliferation and Apoptosis and Hedgehog Pathway of Diffuse Large B-Cell Lymphoma Cells

作　　者：王玲[1] 丁世权 李华伟[3] 杜圣红 陈晨[1] 刘玉玉[1] 李斑斑[1] 刘聪[1] 焦俊 滕清良[1] WANG Ling;DING Shi-Quan;LI Hua-Wei;DU Sheng-Hong;CHEN Chen;LIU Yu-Yu;LI Ban-Ban;LIU Cong;JIAO Jun;TENG Qing-Liang(Department of Hematology,Taian City Central Hospital,Taian 271000,Shandong Province,China;Shandong First Medical University&Shandong Academy of Medical Sciences,Jinan 250000,Shandong Province,China;Department of Information Center,Taian City Central Hospital,Taian 271000,Shandong Province,China)

机构地区：[1]山东省泰安市中心医院血液科,山东泰安271000 [2]山东第一医科大学(山东省医学科学院),山东济南250000 [3]山东省泰安市中心医院信息中心,山东泰安271000

出　　处：《中国实验血液学杂志》2021年第5期1504-1509,共6页Journal of Experimental Hematology

基　　金：山东省自然科学基金(ZR2015HL034);山东省医药卫生科技发展计划面上项目(2019WS212);泰安市科技发展计划(2019NS139)。

摘　　要：目的:探讨二硫化二砷联合伊曲康唑对弥漫大B细胞淋巴瘤细胞增殖和凋亡的作用以及Hedgehog信号通路的影响。方法:将不同浓度的二硫化二砷和伊曲康唑与弥漫大B细胞淋巴瘤细胞株OCI-LY3共培养。采用CCK-8方法检测细胞增殖情况;AnnexinⅤ-PI方法检测细胞凋亡率;Western blot检测BCL-2、BAX、SM0、Glil蛋白的表达水平。结果:伊曲康唑与弥漫大B细胞淋巴瘤细胞株OCI-LY3共培养24、48和72 h后,细胞活力随作用时间的延长明显下降。随着伊曲康唑浓度的增加,OCI-LY3细胞活力较对照组明显降低(r=-0.690,r=-0.639,r=-0.833,r=-0.808,r=-0.578)。联合用药与单药组相比,OCI-LY3细胞增殖抑制作用更明显,且OCI-LY3细胞凋亡率明显升高(P<0.05)。经二硫化二砷和伊曲康唑作用后,SMO和Glil蛋白表达水平明显下调(P<0.01),与单药组相比,联合用药组SMO和Gli1蛋白表达水平显著降低(P<0.01)。结论:伊曲康唑能以时间和剂量依赖的方式抑制弥漫大B细胞淋巴瘤细胞OCI-LY3生长;二硫化二砷和伊曲康唑联用具有协同作用,能显著下调Hedgehog信号通路中SMO和Glil蛋白表达。Objective:To investigate the effect of arsenic disulfide(As_(2) S_(2))combined with itraconazole on the proliferation,apoptosis and hedgehog pathway of diffuse large B-cell lymphoma(DLBCL)cells.Methods:The human DLBCL cell OCI-LY3 was treated with different concentrations of As_(2) S_(2) and itraconazole.Cell proliferation inhibition was detected by CCK-8,cell apoptosis rate was determined by flow cytometry.The expression levels of BCL-2,BAX,SMO and GLi1 were detected by Western blot.Results:The DLBCL cell viability was decreased significantly at 24,48 or 72 h as cultured with itraconazole.Along with the increasing of itraconazole concentration,the DLBCL cell viability was significantly reduced as compared with that in control group,and the results showed statistically significant(r=-0.690,r=-0.639,r=-0.833,r=-0.808,r=-0.578).The inhibitory and apoptosis rates of the cells were significantly increased as compared with those of the single drug-treated group after treated by the combination of itraconazole and As2 S2(P<0.05).The protein levels of SMO and Glil were significantly down-regulated after treated by arsenic disulfide and itraconazole alone(P<0.01).The protein expression levels of SMO and Glil was down-regulated in the combinedtreatment group(P<0.01).Conclusion:Itraconazole can inhibit proliferation of DLBCL cells in a concentration-and time-dependent manner.In addition,the combination of As2 S2 and itraconazole show a synergistic effects,which may be related with the down-regulated protein expression of SMO and Glil of Hedgehog signaling pathway.

关 键 词：二硫化二砷 伊曲康唑 弥漫大B细胞淋巴瘤 凋亡 Hedgehog信号 

分 类 号：R733.1[医药卫生—肿瘤]