车叶草苷通过内质网应激促进胰腺癌细胞凋亡的机制研究  

Study on apoptosis of pancreatic cancer cells induced by asperuloside through endoplasmic reticulum stress

作　　者：曹龄之 付国旭 陈飞[1] 李素平[1] 杨凡慧 CAO Ling-zhi;FU Guo-xu;CHEN Fei;LI Su-ping;YANG Fan-hui(Department of Nuclear Medicine,1.Affiliated Hospital of North Sichuan Medical College,Nanchong 637000;The Third Hospital of Mianyang,Mianyang 621000,Sichuan,China)

机构地区：[1]川北医学院附属医院核医学科,四川南充637000 [2]绵阳市第三人民医院核医学科,四川绵阳621000

出　　处：《川北医学院学报》2023年第11期1469-1474,共6页Journal of North Sichuan Medical College

基　　金：四川省科技厅健康重大专项(2022ZDZX0023);四川省科技厅项目(2021YJ0515);四川省医学会项目(Q22046)。

摘　　要：目的:探讨车叶草苷(ASP)通过内质网应激(ERS)诱导胰腺癌(PC)细胞凋亡的机制。方法:选取人胰腺癌PANC-1细胞作为研究对象。将PANC-1细胞按照随机数字表法分为4组,分别为对照组、ASP组、ERS抑制剂4-苯基丁酸(4-Phenylbutyric acid,4-PBA)组和ASP+4-PBA组。采用CCK-8检测细胞增殖情况,采用流式细胞术检测细胞凋亡情况,Transwell法检测细胞迁移,蛋白质印迹法检测细胞中活化转录因子6(ATF6)、C/BEP环腺苷酸反应元件结合转录因子同源蛋白(CHOP)、活化的半胱氨酸蛋白酶3(cleaved-caspase 3)、蛋白激酶R样内质网激酶(PERK)及肌醇依赖性激酶1α磷酸化蛋白(p-IRE1α)相对表达水平。结果:随着ASP浓度的增加,PANC-1细胞增殖率呈下降趋势。与对照组相比,ASP组迁移细胞数量降低,细胞凋亡率增加,ATF6、CHOP、cleaved-caspase-3、PERK及p-IRE1α蛋白相对表达水平上升,差异均有统计学意义(P<0.05)。与ASP组相比,ASP+4-PBA组细胞迁移数量增多、细胞凋亡率下降(P<0.05),ATF6、CHOP、cleaved-caspase-3、PERK及p-IRE1α蛋白相对表达水平下降,差异均有统计学意义(P<0.05)。结论:ASP能够从细胞增殖、迁移、凋亡三个方面降低胰腺癌细胞活性,其作用机制可能与激活ERS有关。Objective:To investigate the mechanism of apoptosis in pancreatic cancer(PC)cells induced by Asperuloside(ASP)through endoplasmic reticulum stress(ERS).Methods:Human pancreatic cancer PANC-1 cells were selected as the study subjects.PANC-1 cells were divided into four groups:control group(conventional culture),ASP group,ERS inhibitor 4-Phenylbutyric acid group(4-PBA group)and ASP+4-PBA group according to the random number table methods.Cell proliferation was detected by cell counting kit-8(CCK-8),apoptosis was detected by flow cytometry,migration was measured by Transwell,and activating transcription factor 6(ATF6),C/EBP homologus protein(CHOP),cleaved-caspase-3,protein kinase-like ER kinase(PERK)and p-IRE1αprotein relative expression levels were detected by Western blot.Results:The proliferation rate of PANC-1 cells decreased with the increase of ASP concentration.Compared with the control group,the number of migrating and invading cells decreased,the apoptosis rate increased,and the relative expression levels of ATF6,CHOP,cleaved-caspase-3,PERK and p-IRE1αproteins increased in the ASP group,with statistically significant differences(P<0.05).Compared with the ASP group,the ASP+4-PBA group showed an increase in cell migration and a decrease in cell apoptosis rate(P<0.05).The relative expression level of ATF6,CHOP,cleared caspase-3,PERK,and p-IRE1αproteins decreased,and the differences were statistically significant(P<0.05).Conclusion:ASP can reduce the activity of PANC-1 cells from the aspects of cell proliferation,migration and apoptosis,and its mechanism may be related to the activation of ERS.

关 键 词：胰腺癌 车叶草苷 内质网应激 细胞凋亡 

分 类 号：R735.9[医药卫生—肿瘤]