来那度胺抑制PD1/PD-L1信号调节淋巴细胞对HepG2的免疫杀伤作用

Lenalidomide Inhibits the PD1/PD-L1 Signal to Regulate the Immune Killing Effect of Lymphocyte on HepG2

关键词:  来那度胺  PD1/PD-L1  淋巴细胞

Key words:  lenalidomide  PD1/PD-L1  lymphocytes

摘要:

目的 探究来那度胺抑制PD1/PD-L1信号增强淋巴细胞杀伤HepG2的能力。方法 提取人淋巴细胞与HepG2共培养，流式细胞术检测HepG2的凋亡，CCK-8检测HepG2的活力，Western blot检测PD-L1/PD-1表达，Elisa法检测IL-2、IL-12、TNF-α的表达。构建HepG2的荷瘤小鼠模型，来那度胺干预后，计算抑瘤率，Western blot检测小鼠肿瘤组织中PD-1和PD-L1的表达，qPCR检测肿瘤组织中IL-2、IL-12和TNF-α的mRNA表达。结果 来那度胺可以增加淋巴细胞对于HepG2的杀伤能力，HepG2凋亡率显著增高，PD-1和PD-L1表达下降。IL-2、IL-12和TNF-α表达增高。来那度胺对于荷瘤小鼠有明显的肿瘤抑制作用，可以降低肿瘤组织中PD-1和PD-L1表达，IL-2、IL-12和TNF-α的mRNA表达增高。结论 来那度胺抗肿瘤作用与其免疫调节有关，来那度胺可以通过抑制PD-1/PD-L1信号增强淋巴细胞对HepG2的杀伤作用。

Abstract:

OBJECTIVE To investigate the inhibitory effect of lenalidomide on PD1/PD-L1 to enhance lymphocyte killing effect of HepG2. METHODS Human lymphocytes were co-cultured with HepG2, flow cytometry was used to detect the apoptosis of HepG2, CCK-8 detected HepG2 activity, Western blot was used to detect PD-L1/PD-1 expression. The expression of IL-2, IL-12 and TNF-α was detected by Elisa method. To construct mouse model of HepG2, after lenalidomide intervention, calculated the tumor inhibition rate, Western blot was used to detect the expression of PD-1 and PD-L1 in mouse carcinoma, qPCR was used to detect the mRNA expression of IL-2, IL-12 and TNF-α in cancer tissues. RESULTS Lenalidomide could increase the ability of lymphocytes to kill HepG2, HepG2 apoptosis rate was significantly increased, PD-1 and PD-L1 expression decreased, IL-2, IL-12 and TNF-α expression were increased. Lenalidomide had a significant tumor inhibitory effect on mice, it could reduce the expression of PD-1 and PD-L1 in tumor tissue, and increased IL-2, IL-12 and TNF-α mRNA expression. CONCLUSION The anti-tumor effect of lenalidomide is related to its immune regulation, Lenalidomide can inhibit PD-1/PD-L1 to enhance lymphocyte killing of HepG2。