首页|程序性死亡配体-1抑制剂对神经胶质瘤细胞的抑制作用及其机制

程序性死亡配体-1抑制剂对神经胶质瘤细胞的抑制作用及其机制

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目的 探讨程序性死亡配体-1(PD-L1)抑制剂对神经胶质瘤细胞恶性生物学行为的抑制作用及其作用机制。方法 选取人正常星形胶质细胞HA1800和人神经胶质瘤细胞U87-MG、U251-MG作为研究对象,实时荧光定量聚合酶链反应检测HA1800、U87-MG、U251-MG细胞PD-L1 mRNA表达水平;U87-MG细胞分为两组,分别是添加PD-L1抑制剂的U87-MG细胞(实验组)和未经PD-L1抑制剂处理的U87-MG细胞(对照组)。采用细胞计数试剂盒(CCK-8)检测实验组和对照组细胞的增殖活力;采用Transwell小室检测实验组和对照组细胞的迁移与侵袭能力;采用蛋白免疫印迹检测实验组和对照组细胞PD-L1、信号传导及转录激活蛋白1(STAT1)和信号传导及转录激活蛋白3(STAT3)磷酸化水平。组间比较采用t检验。结果 U87-MG细胞(1。73±0。08)和U251-MG细胞(1。62±0。06)中PD-L1 mRNA的表达水平明显高于HA1800细胞(0。49±0。05),差异有统计学意义(t=31。91、37。70,P<0。05)。实验组细胞(0。52±0。05、0。82±0。04)在第48、72小时的吸光度(A)值明显低于对照组细胞(0。80±0。05、1。32±0。06),差异有统计学意义(t=9。49、17。94,P<0。05)。实验组细胞迁移细胞数[(73。33±5。35)个]和侵袭细胞数[(46。17±5。12)个]明显低于对照细胞[(135。17±7。52)、(88。50±6。77)个],差异有统计学意义(t=16。41、12。21,P<0。05)。实验组细胞PD-L1蛋白水平(0。88±0。05)、STAT3磷酸化水平(0。44±0。05)明显低于对照组细胞(1。88±0。06、1。24±0。05),差异有统计学意义(t=30。34、26。73,P<0。05)。实验组细胞 STAT1 磷酸化水平(1。32±0。08)明显高于对照组细胞(0。51±0。05),差异有统计学意义(t=20。43,P<0。05)。结论 PD-L1抑制剂可通过上调磷酸化STAT1水平、下调STAT3磷酸化水平,抑制神经胶质瘤细胞的增殖、迁移和侵袭。
Inhibitory effect of programmed cell death ligand-1 inhibitor on neuroglioma cells and its mecha-nism
Objective To investigate the inhibitory effect of programmed cell death ligand-1(PD-L1)inhibitor on malignant biological behavior of neuroglioma cells and its mechanism.Methods Human normal astrocytes HA 1800 and human neuroglioma cells(U87-MG,U251-MG)were selected for the study.Real-time fluorescence quantitative polymerase chain reaction was used to detect the PD-L1 mRNA expression in HA1800,U87-MG,and U251-MG cells.U87-MG cells were divided into two groups:U87-MG cells with the addition of PD-L1 inhibitor(experimental group)and U87-MG cells without PD-L1 inhibitor treatment(control group).The cell proliferation viability in the experimental and control groups was detected using a cell counting kit-8(CCK-8)assay;Transwell was used to detect the migration and in-vasion ability of the experimental group and the control group.The protein expression of PD-L1,phospho-rylation signal transducer and activators of transcription 1(STAT1),and phosphorylation signal transducer and activators of transcription 3(STAT3)in the experimental group and control group was detected by Western blotting.The t-test was used for comparison between groups.Results The expression of PD-L1 mRNA in U87-MG cells(1.73±0.08)and U251-MG cells(1.62±0.06)was significantly higher than that in HA1800 cells(0.49±0.05,t=31.91,37.70,P<0.05).The absorbance(A)value of the experi-mental group(0.52±0.05,0.82±0.04)at 48 h and 72 h was significantly lower than that of the control group(0.80±0.05,1.32±0.06,t=9.49,17.94,P<0.05).The number of migrating cells[(73.33±5.35)]and invasive cells[(46.17±5.12)]in the experimental group was significantly less than that in the control group[(135.17±7.52)and(88.50±6.77),t=16.41,12.21,P<0.05].The protein ex-pression of PD-L1(0.88±0.05)and phosphorylated STAT3(0.44±0.05)in experimental group was sig-nificantly lower than that in control group(1.88±0.06,1.24±0.05,t=30.34,26.73,P<0.05).The phosphorylated STAT1 in experimental group(1.32±0.08)was significantly higher than that in control group(0.51±0.05,t=20.43,P<0.05).Conclusion PD-L1 inhibitor can inhibit the proliferation,mi-gration and invasion of programmed cells by up-regulating the phosphorylated STAT1 and down-regulating the phosphorylated STAT3.

Programmed cell death ligand-1 inhibitorNeurogliomaProliferationMigrationInvasion

申法政、崔士娟、梁甲宁、王向阳、孟磊、马继伟、赵新利

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新乡医学院第一附属医院神经外科,卫辉 453100

新乡医学院第一附属医院结核内科,卫辉 453100

程序性死亡配体-1抑制剂 神经胶质瘤 增殖 迁移 侵袭

河南省医学科技攻关计划项目

LHGJ20210515

2024

中华实验外科杂志
中华医学会

中华实验外科杂志

CSTPCD
影响因子:0.759
ISSN:1001-9030
年,卷(期):2024.41(7)
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