>
网站首页期刊介绍通知公告编 委 会投稿须知电子期刊广告合作联系我们
最新消息:
ERS标志物PDI表达对肝癌细胞迁移的影响
作者:李利波1  曹辉1  张红丽1  潘娅2 
单位:1. 贵州省人民医院 肿瘤科, 贵州 贵阳 550002;
2. 贵州医科大学, 贵州 贵阳 550002
关键词:肝癌细胞 内质网应激 蛋白质二硫键异构酶 肿瘤转移 
分类号:R735.7;Q558
出版年·卷·期(页码):2018·37·第五期(782-788)
摘要:

目的:研究内质网应激(ERS)标志物蛋白质二硫键异构酶(PDI)表达对肝癌细胞迁移的影响。方法:取人正常肝细胞株LO2、肝癌细胞株HepG2和SMMC-7721,采用无水乙醇处理48 h诱导发生ERS;采用Western blotting检测葡萄糖调节蛋白78(GRP78)、生长停滞及DNA损伤诱导基因153(CHOP)、X-盒-结合蛋白-1(XBP-1)及PDI的表达水平;观察PDI过表达对肝癌细胞迁移能力的影响。结果:Western blotting结果显示,与醇处理前比较,处理后的细胞GRP78及XBP-1表达水平升高(P<0.05);LO2和SMMC-7721中CHOP含量显著上调(P<0.05),但HepG2均无CHOP表达。在处理48 h后,3种细胞中PDI的表达水平均下调,表达水平从高到低为SMMC-7721、LO2、HepG2,与处理前相比较,差异有统计学意义(P<0.05)。PDI过表达后,LO2的迁移能力降低,HepG2和SMMC-7721的迁移能力增强(P<0.05)。结论:无水乙醇诱导ERS后,PDI在SMMC-7721及HepG2中表达水平下调;PDI表达水平与上述两种肝癌细胞迁移能力相关,即PDI过表达可促进HepG2与SMMC-7721迁移。

Objective:To study the effects of endoplasmic reticulum stress(ERS) marker protein disulfide isomerase (PDI) expression on liver cancer cell migration. Methods:The human normal liver cell line LO2, liver cancer cell line HepG2 and high transfer capability hepatocellular carcinoma cell line SMMC-7721 were taken, anhydrous ethanol was used to induce ERS for 48 h. Western blotting was used to detect ERS marker glucose regulation protein 78 (GRP78), stunted growth and DNA damage induced by gene 153 (CHOP), X-box-binding protein 1 (XBP-1) and the expression level of PDI. The effect of PDI overexpression on the migration ability of HCC cells was observed. Results:Western blotting results showed that compared with prior to anhydrous ethanol treatment, the expression of GRP78 and XBP-1 levels were rised (P<0.05) after treatment; CHOP content in SMMC-7721 and LO2 cells was significantly raised (P<0.05), But HepG2 was not expressed in CHOP before and after anhydrous ethanol processing. After anhydrous ethanol processing for 48 h, PDI expression of three cells was down, the sequencel of PDI in expression from high to low was SMMC-7721, LO2, HepG2. Compared with that before anhydrous ethanol processing, the difference was statistically significant (P<0.05).After PDI overexpression, LO2 cell migration ability was reduced, HepG2 and SMMC-7721 cell migration ability were enhanced (P<0.05). Conclusion:After ERS induced by ethanol, PDI expression level in SMMC-7721 and HepG2 cells are cut. PDI expression level is associated with the above two kinds of liver cancer cell migration ability.The PDI expression can promote HepG2 and SMMC-7721 migration.

参考文献:

[1] RODRIGUES L M R,THEODORO T R,MATOS L L,et al.Heparanase isoform expression and extracellular matrix remodeline in intervertebral disc degenerative disease clinics[J].Clinics (Sao Paulo),2011,66(5):903-909.
[2] 董凯楠,黄忻,邢文英.内质网应激对胃癌细胞迁移与侵袭的影响[J].世界华人消化杂志,2016,24(10):1485-1491.
[3] 范威,潘翠萍,张懿敏,等.内质网应激对乳腺癌MCF-7细胞CCL5表达的影响[J].肿瘤防治研究,2012,39(4):385-388.
[4] 金学英,汪步海.内质网应激和肿瘤[J].东南大学学报(医学版),2013,32(1):110-114.
[5] WANG Y,ALAM G N,NING Y.The unfolded protein response induces the angiogenic switch in human tumor cells through the PERK/ATF4 pathway[J].Cancer Res,2012,72(20):5396-5406.
[6] HOU M,JACOB A,HO N,et al.Downregulation of protein disulfide isomerase in sepsis and its role in tumor necrosis factor-alpha release[J].Crit Care,2008,12:R100.
[7] GOPLEN D,WANG J,ENGER P O,et al.Protein disulfide isomerase expression is related to the invasive properties of malignant glioma[J].Cancer Res,2006,66:9895-9902.
[8] HENDERSHOT L M.The ER function BiP is a master regulat or of ER function[J].Mt Sinai J Med,2004,71(5):289-297.
[9] TABATA Y,TAKANO K,ITO T,et al.Vaticanol B,a resveratrol tetramer,regulates endoplasmic reticulum stress and inflammation[J].Am J Physiol Cell Physiol,2007,293:C411-C418.
[10] HSU T A,WATSON S,EIDEN J J,et a1.Rescue of immunoglobulins from insolubility is facilitated by PDI in the baculovirus expression system[J].Protein Expr Purif,1996,7:281-288.
[11] ZHENG H C,TAKAHASHI H,LI X H,et al.Overexpression of GRP78 and GRP94 are markers for aggressive behavior and poor prognosis in gastric carcinomas[J].Hum Pathol,2008,39:1042-1049.
[12] XU S,SANKAR S,NEAMATI N.Protein disulfide isomerase:a promising target for cancer therapy[J].Drug Discov Today,2014,19:222-240.
[13] PESCATORE L A,BONATTO D,FORTI F L,et al.Protein disulfide isomerase is required for platelet-derived growth factor-induced vascular smooth muscle cell migration,Nox1 NADPH oxidase expression and Rho GTPase activation[J].J Biol Chem,2012,287(35):29290-29300.
[14] KURTOGLU M,PHILIPS K,LIU H,et al.High endoplasmic reticulum activityrenders multiple myeloma cells hypersensitive to mitochondrial inhibitors[J].Cancer Chemother Pharmacol,2010,66:129-140.
[15] SIEGEL R L,MILLER K D,JEMAL A.Cancer Statistics,2017[J].CA Cancer J Clin,2017,67(1):7-30.
[16] CHEN W, ZHENG R, BAADE P D, et al.Cancer Statistics in China,2015[J].CA Cancer J Clin, 2016,66(2):115-132.
[17] 魏矿荣,彭侠彪,梁智恒,等.全球肝癌流行概况[J].中国肿瘤,2015,24(8):621-630.
[18] 黄赞松,仇仪英,周喜汉.原发性肝癌现代医学治疗的研究进展[J].医学综述,2012,18(24):4169-4172.
[19] ALLAVENA P,SICA A,GARLANDA C,et al.The Yin-Yang of tumor-associated macrophages in neoplastic progression and immune surveillance[J].Immunol Rev,2008,222(12):155-161.
[20] MAHADEVAN N R,RODVOLD J,SEPULVEDA H,et al.Transmission of endoplasmic reticulum stress and pro-inflammation from tumor cells to myeloid cells[J].Proc Natl Acad Sci USA,2011,108:6561-6566.
[21] 邓志华,黄赞松.microRNA与消化系统肿瘤[J].生物医学工程与临床,2011,15(5):493-497.
[22] BENHAM A M.The protein disulfide isomerase family:key players in health and disease[J].Antioxid Redox Signal,2012,16:781-789.
[23] LOVAT P E,CORAZZARI M,ARMSTRONG J L,et al.Increasing melanoma cell death using inhibitors of protein disulfide isomerases to abrogate survival responses to endoplasmic reticulum stress[J].Cancer Res,2008,68(13):5363-5369.
[24] GORLACH A,KLAPPA P,KIETZMANN T.The endoplasmic reticulum:folding,calcium homeostasis,signaling,and redox control[J].Antioxid Redox Signal,2006,8(9-10):1391-1418.
[25] TU B P,WEISSMAN J S.Oxidative protein folding in eukaryotes:mechanisms and consequences[J].J Cell Biol,2004,164(3):341-346.
[26] SEVIER C S,KAISER C A.Ero1 and redox homeostasis in the endoplasmic reticulum[J].Biochim Biophys Acta,2008,1783(4):549-556.
[27] GILLECE P,LUZ J M,LENNARZ W J,el at.Export of a cysteine-free misfolded secretory protein from the endoplasmic reticulum for degradation requires interaction with protein disulfide isomerase[J].J Cell Biol,1999,147:1443-1456.
[28] 刘宏,顾页,蔡盈盈,等.蛋白赖氨酸甲基转移酶SET7/9表达对肝癌细胞增殖、凋亡和迁移的影响[J].东南大学学报(医学版),2017,36(3):351-356.
[29] 张玮,申文豪,李阳,等.三七总皂苷联合顺铂对肝癌细胞HepG2和SMMC-7721增殖、迁移、侵袭及凋亡的影响[J].东南大学学报(医学版),2017,36(3):383-389.

服务与反馈:
文章下载】【发表评论】【查看评论】【加入收藏
提示:您还未登录,请登录!点此登录
您是第 152989 位访问者


copyright ©《东南大学学报(医学版)》编辑部
联系电话:025-87232483 83272481
电子邮件:
bjb@pub.seu.edu.cn

苏ICP备09058364