PD-L1反义寡核苷酸纳米颗粒对胃癌细胞侵袭和免疫因子分泌作用  

Effects of PD-L1 Antisense Oligonucleotide Nanoparticles on the Invasion and Immune Factor Secretion of Gastric Cancer Cells

作　　者：赵鸿鹰 江荣科 李艳芳[1] 朱梅[1] 王雪[1] Zhao Hongying;Jiang Rongke;Li Yanfang;Zhu Mei;Wang Xue(Xuzhou Cancer Hospital,Xuzhou Third Peolpe’s Hospital,Affiliated Hospital of Jiangsu University,Jiangsu Xuzhou 221000,China)

机构地区：[1]徐州市肿瘤医院、徐州市第三人民医院、江苏大学附属徐州医院,江苏徐州221000

出　　处：《中国药师》2022年第12期2067-2073,共7页China Pharmacist

摘　　要：目的:探讨细胞程序性死亡蛋白配体1(PD-L1)反义寡核苷酸纳米颗粒对胃癌细胞侵袭和免疫因子分泌的作用。方法:人胃癌细胞AGS分成对照(Control)组、聚氰基丙烯酸丁酷纳米粒(PBCA-NP)组、PD-L1正义寡核苷酸(SOND)组、PD-L1反义寡核苷酸(ASOND)组、PD-L1反义寡核苷酸纳米颗粒(ASOND-NP)组、ASOND-NP+胰岛素样生长因子1(IGF-1)组,采用Western Blot法检测PD-L1、磷酸化的磷脂酰肌醇3-激酶(p-PI3K)、PI3K、磷酸化的苏氨酸激酶(p-AKT)、AKT、B淋巴细胞瘤-2基因(Bcl-2)、Bcl-2相关X蛋白(Bax)、增殖细胞核抗原(PCNA)、基质金属蛋白酶2(MMP-2)、基质金属蛋白酶9(MMP-9)蛋白的表达,细胞计数试剂盒(CCK-8)检测细胞增殖活性,流式细胞术检测细胞凋亡率,Transwell小室检测细胞迁移和侵袭,ELISA法检测血管内皮生长因子(VEGF)、转化生长因子-β(TGF-β)、白细胞介素-6(IL-6)水平。结果:与Control组和SOND组比较,ASOND组胃癌细胞中PD-L1、p-PI3K/PI3K、p-AKT/AKT蛋白表达减少,细胞增殖活性降低,细胞凋亡率升高,Bax蛋白表达增多,Bcl-2、PCNA蛋白表达减少,细胞侵袭数目、迁移数目和MMP-2、MMP-9蛋白表达均减少,细胞分泌的VEGF、TGF-β、IL-6均减少(P<0.05);与PBCA-NP组和ASOND组比较,ASOND-NP组胃癌细胞中PD-L1、p-PI3K/PI3K、p-AKT/AKT蛋白表达减少,细胞增殖活性降低,细胞凋亡率升高,Bax蛋白表达增多,Bcl-2、PCNA蛋白表达减少,细胞侵袭数目、迁移数目和MMP-2、MMP-9蛋白表达均减少,细胞分泌的VEGF、TGF-β、IL-6均减少(P<0.05);与ASOND-NP组比较,ASOND-NP+IGF-1组胃癌细胞中p-PI3K/PI3K、p-AKT/AKT蛋白表达增多,细胞增殖活性升高,细胞凋亡率降低,Bax蛋白表达减少,Bcl-2、PCNA蛋白表达增多,细胞侵袭数目、迁移数目和MMP-2、MMP-9蛋白表达均增多,细胞分泌的VEGF、TGF-β、IL-6均增多(P<0.05)。结论:PD-L1反义寡核苷酸纳米颗粒通过抑制PI3K/AKT信号抑制胃癌细胞侵袭、迁移并减少免�Objective: To investigate the effects of PD-L1 antisense oligonucleotide nanoparticles on the invasion and immune factor secretion of gastric cancer cells. Methods: Human gastric cancer cells AGS were divided into control group, polybutylene cyanoacrylate nanoparticles(PBCA-NP) group, PD-L1 sense oligonucleotide(SOND) group, PD-L1 antisense oligonucleotide(ASOND) group, PD-L1 antisense oligonucleotide nanoparticles(ASOND-NP) group and ASOND-NP+IGF-1 group. The expression of PD-L1, p-PI3 K, PI3 K, p-AKT, AKT, Bax, Bcl-2, PCNA, MMP-2 and MMP-9 proteins were detected by Western blot, the cell proliferation was detected by cell counting kit(CCK-8), the apoptosis rate was detected by flow cytometry, the Transwell cell was used to detect cell migration and invasion, and the levels of VEGF, TGF-β and IL-6 were detected by ELISA. Results: Compared with those in the control group and SOND group, the expression of PD-L1, p-PI3 K/PI3 K and p-AKT/AKT proteins in gastric cancer cells in ASOND group decreased, the cell proliferation activity decreased, the apoptosis rate increased, the expression of Bax protein increased, and the expression of Bcl-2 and PCNA proteins, number of cell invasion and migration, expression of MMP-2 and MMP-9 proteins, and secretion of VEGF, TGF-β and IL-6 by cells were decreased(P<0.05). Compared with those in PBCA-NP group and ASOND group, the expression of PD-L1, p-PI3 K/PI3 K and p-AKT/AKT proteins in gastric cancer cells in ASOND-NP group decreased, the cell proliferation activity decreased, the apoptosis rate increased, the expression of Bax protein increased, and the expression of Bcl-2 and PCNA proteins, number of cell invasion and migration, expression of MMP-2 and MMP-9 proteins, and secretion of VEGF, TGF-β and IL-6 by cells were decreased(P<0.05). Compared with those in ASOND-NP group, the expression of p-PI3 K/PI3 K and p-AKT/AKT proteins in gastric cancer cells in ASOND-NP+IGF-1 group increased, the cell proliferation activity increased, the apoptosis rate decreased, the expression o

关 键 词：程序性死亡蛋白配体1 纳米颗粒 胃癌 免疫因子 侵袭 

分 类 号：R965.1[医药卫生—药理学]