基于GRP78/PERK/CHOP通路探讨车叶草苷对胰腺癌细胞增殖、凋亡的影响  

Influences of Asperuloside on prolif eration and apoptosis of pancreatic cancer cells based on GRP78/PERK/CHOP pathway

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

机构地区：[1]川北医学院附属医院核医学科,637000 [2]绵阳第三人民医院核医学科,621000

出　　处：《现代消化及介入诊疗》2022年第10期1282-1287,共6页Modern Interventional Diagnosis and Treatment in Gastroenterology

基　　金：川北医学院校级课题(CBY20-QA-Y22)。

摘　　要：目的探究车叶草苷(Asperuloside,Asp)通过调节葡萄糖调节蛋白78(glucose-regulated protein 78,GRP78)/蛋白激酶R样内质网激酶(protein kinase R-like ER kinase,PERK)/CCAAT/增强子结合蛋白同源蛋白(CCAAT/enhancer binding protein homologous protein,CHOP)信号通路对胰腺癌细胞增殖、凋亡的影响。方法收集42例胰腺癌组织及其癌旁的正常组织,并将胰腺癌组织分为24例转移组织和18例未转移组织。将sw1990细胞分为sw1990组(未作任何处理的sw1990细胞)、L-Asp组(1 mmol/L Asp)、M-Asp组(2 mmol/L Asp)、H-Asp组(3 mmol/L Asp)、4-PBA组(3 mmol/L Asp+1 mmol/L 4-PBA处理sw1990细胞)。CCK-8和Edu检测sw1990细胞增殖;流式细胞术检测sw1990细胞凋亡;划痕实验检测细胞迁移率;Transwell法检测sw1990细胞侵袭;Western blot检测上皮间质转化(EMT)蛋白、自噬、凋亡蛋白以及通路相关蛋白水平。结果正常组织、无转移的胰腺癌组织、有转移的胰腺癌组织GRP78、PERK、p-CHOP/CHOP蛋白水平依次显著降低(P<0.05)。与sw1990组相比,L-Asp组、M-Asp组、H-Asp组的sw1990细胞生长率、阳性率、迁移率以及侵袭细胞数量、vimentin、Twist1、Bcl-2蛋白水平依次显著下降(P<0.05),细胞凋亡率、E-cadherin、Bax、cleaved-Caspase-12、GRP78、PERK、p-CHOP/CHOP、Beclin1、LC3-II/I蛋白水平依次显著升高(P<0.05);与H-Asp组相比,4-PBA组sw1990细胞生长率、阳性率、迁移率以及侵袭细胞数量、vimentin、Twist1、Bcl-2蛋白水平显著上升(P<0.05),细胞凋亡率、E-cadherin、Bax、cleaved-Caspase-12、GRP78、PERK、p-CHOP/CHOP、Beclin1、LC3-II/I蛋白水平依次显著下降(P<0.05)。结论Asp可能通过上调GRP78/PERK/CHOP信号通路来抑制胰腺癌细胞的增殖,促进其凋亡。Objective To investigate the influences of Asperuloside(Asp)on the proliferation and apoptosis of pancreatic cancer cells by regulating the glucose regulated protein 78(GRP78)/protein kinase R-like endoplasmic reticulum kinase(PERK)/CCAAT enhancer binding protein(CHOP)signaling pathway.Methods Forty-two cases of pancreatic cancer tissues and their adjacent normal tissues were collected,and the pancreatic cancer tissues were divided into 24 cases of metastatic tissues and 18 cases of non metastatic tissues.The sw1990 cells were divided into sw1990 group(sw1990 cells without any treatment),L-Asp group(1 mmol/L Asp),M-Asp group(2 mmol/LAsp),H-Asp group(3 mmol/L Asp),4-PBA group(sw1990 cells were treated with 80μmol/L Asp+1 mmol/L 4-PBA).The proliferation of sw1990 cells was detected by CCK-8 and Edu;apoptosis of sw1990 cells was detected by flow cytometry;the cell migration rate was detected by scratch test;Transwell method was used to detect the invasion of sw1990 cells;Western blot was used to detect the levels of epithelial mesenchymal transformation(EMT)protein,autophagy,apoptosis protein and pathway related protein.Results The protein levels of GRP78,PERK,p-CHOP/CHOP in normal tissues,non metastatic pancreatic cancer tissues,and metastatic pancreatic cancer tissues decreased obviously in turn(P<0.05).Compared with sw1990 group,the growth rate,positive rate,migration rate of sw1990 cells,the number of invasive cells,the protein levels of vimentin,Twist1,and Bcl-2 in L-Asp group,M-Asp group,and H-Asp group decreased obviously in turn(P<0.05),the apoptosis rate,the protein levels of E-cadherin,Bax,cleaved Casase-12,GRP78,PERK,p-CHOP/CHOP,Beclin1,and LC3-II/I increased obviously in turn(P<0.05);compared with H-Asp group,the growth rate,positive rate,migration rate of sw1990 cells,the number of invasive cells,the protein levels of vimentin,Twist1,and Bcl-2 in 4-PBA group increased obviously(P<0.05),the apoptosis rate,the protein levels of E-cadherin,Bax,cleaved Casase-12,GRP78,PERK,p-CHOP/CHOP,Beclin1,and LC3-II/I

关 键 词：车叶草苷 GRP78/PERK/CHOP信号通路 胰腺癌 增殖 凋亡 

分 类 号：Q95-3[生物学—动物学] R576[医药卫生—消化系统]