PI3K抑制剂idelalisib对弥漫性大B细胞淋巴瘤细胞株细胞因子及PD-L1表达的影响  

Effect of PI3K inhibitor idelalisib on the expression of cytokines and PD-L1 in diffuse large B-cell lymphoma cell lines

作　　者：程珍 白雪 饶彪锋 邵红 李春溟 严敏[1] 潘湘涛[1] 陆晔[1] CHENG Zhen;BAI Xue;RAO Biaofeng;SHAO Hong;LI Chunming;YAN Min;PAN Xiangtao;LU Ye(Department of Hematology,Affiliated Taicang Hospital of Soochow University,the First People’s Hospital of Taicang,Jiangsu Province,Suzhou215400,China)

机构地区：[1]苏州大学附属太仓医院太仓市第一人民医院血液科,江苏苏州215400

出　　处：《中国医药导报》2024年第31期42-46,51,共6页China Medical Herald

基　　金：江苏省苏州市“科教强卫”青年科技项目(KJXW2019062)。

摘　　要：目的研究磷脂酰肌醇3-激酶(PI3K)抑制剂对弥漫性大B细胞淋巴瘤(DLBCL)细胞株细胞因子及程序性死亡配体1(PD-L1)表达的影响。方法CCK-8法检测4种DLBCL细胞株对PI3K抑制剂(idelalisib)的敏感性。每种细胞株设对照组(不加药物)与实验组(加15、30μmol/L idelalisib)。RT-qPCR、酶联免疫吸附试验、Western blot法检测各组磷酸化蛋白激酶(pAkt)、细胞因子[白细胞介素(IL)-10、血管内皮生长因子(VEGF)、肿瘤坏死因子-α(TNF-α)]及程序性死亡配体1(PD-L1)表达的变化。结果4种细胞株对idelalisib的敏感性由高到低依次为FARAGE、OCI-LY19、U2932、SU-DHL-8。FARAGE细胞:15、30μmol/L实验组IL-10、VEGF、TNF-α、PD-L1表达量低于对照组(P<0.05)。OCI-LY19细胞:30μmol/L实验组IL-10、TNF-α、PD-L1表达量低于对照组(P<0.05);15μmol/L实验组VEGF、TNF-α表达量低于对照组(P<0.05)。U2932细胞:30μmol/L实验组IL-10表达量高于对照组,VEGF、TNF-α表达量低于对照组(P<0.05);15μmol/L实验组VEGF、TNF-α表达量低于对照组(P<0.05)。SU-DHL-8细胞:30μmol/L实验组IL-10、TNF-α、PD-L1表达量高于对照组(P<0.05);15μmol/L实验组VEGF表达量高于对照组(P<0.05)。FARAGE、OCI-LY19细胞∶15、30μmol/L实验组IL-10、VEGF分泌量低于对照组(P<0.05)。U2932细胞∶15、30μmol/L实验组VEGF分泌量低于对照组(P<0.05)。结论在DLBCL细胞株中,PI3K抑制剂可以通过抑制Akt的磷酸化、减少IL-10、VEGF的分泌,发挥抗肿瘤反应,PI3K/Akt通路在DLBCL中可以促进肿瘤免疫逃逸。Objective To investigate the effect of phosphoinositide 3-kinase(PI3K)inhibitor on the expression of cytokines and programmed death ligand 1(PD-L1)in diffuse large B-cell lymphoma(DLBCL)cell lines.Methods The sensitivity of four DLBCL cell lines to the PI3K inhibitor idelalisib was measured using the CCK-8 assay.Each cell line was divided into control group(without drug treatment)and experimental group(treated with 15,30μmol/L idelalisib).The expression of phosphorylated protein kinase(pAkt),cytokines(interleukin[IL]-10,vascular endothelial growth factor[VEGF],tumor necrosis factor-α[TNF-α])and programmed death ligand 1(PD-L1)in each group were detected by RT-qPCR,enzyme-linked immunosorbent assay,and Western blot.Results The sensitivity of four cell lines to idelalisib was FARAGE,OCI-LY19,U2932,and SU-DHL-8 in order from high to low.FARAGE cells:the expressions of IL-10,VEGF,TNF-α,and PD-L1 in the 15 and 30μmol/L experimental groups were lower than those in the control group(P<0.05).OCI-LY19 cells:the expressions of IL-10,TNF-α,and PD-L1 in 30μmol/L experimental group were lower than those in control group(P<0.05).The expression levels of VEGF and TNF-αin 15μmol/L experimental group were lower than those in control group(P<0.05).U2932 cells:the IL-10 expression in the 30μmol/L experimental group was higher than that in the control group,VEGF and TNF-αwere lower than those in the control group(P<0.05).VEGF and TNF-αin the experimental group were lower than those in the control group at 15μmol/L(P<0.05).SU-DHL-8 cells:the expressions of IL-10,TNF-α,and PD-L1 in 30μmol/L experimental group were higher than those in control group(P<0.05).The expression of VEGF in 15μmol/L experimental group was higher than that in control group(P<0.05).FARAGE and OCI-LY19 cells:the secretion levels of IL-10 and VEGF in 15,30μmol/L experimental group were lower than those in control group(P<0.05).U2932 cells:the VEGF secretion in 15,30μmol/L experimental group was lower than that in control group(P<0.05).Conclusion

关 键 词：PI3K抑制剂 弥漫性大B细胞淋巴瘤 细胞因子 程序性死亡配体1 

分 类 号：R733[医药卫生—肿瘤]