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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
【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。
【Abstract】 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-IRE1α protein 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-IRE1α proteins 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-IRE1α proteins 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.
【Key words】 Pancreatic cancer; Asperuloside; Endoplasmic reticulum stress; Apoptosis;
- 【文献出处】 川北医学院学报 ,Journal of North Sichuan Medical College , 编辑部邮箱 ,2023年11期
- 【分类号】R285
- 【下载频次】63