过氧化物酶-4与胃癌发生发展的相关性Relationship of peroxidase-4 to pathogenesis and progress of gastric cancer
邵明洋;杨静;贾茹涵;李文慧;石大林;韩跃武;
摘要(Abstract):
目的分析过氧化物酶-4(peroxidase-4,Prx4)与胃癌发生发展的相关性。方法利用甲基硝基亚硝基胍(N-methyl-N′-nitro-N-nitrosoguanidine,MNNG)诱导正常胃黏膜细胞GES-1构建癌变细胞模型,通过细胞形态、增殖率、迁移能力及集落形成能力的改变,确定MNNG最适浓度及最适诱变时间;经划痕试验、MTT法、集落形成试验、Western blot法和RT-PCR法进一步检测Prx4与胃黏膜上皮细胞恶性转化过程及转化细胞发展过程的相关性。结果MNNG最适浓度为8×10(-5) mol/L,最适诱变时间为16 h。细胞恶性转化过程中呈现出细胞相对增殖率、迁移能力、集落形成能力整体升高的趋势;Prx4蛋白表达水平在0~16 h逐渐升高,16~24 h有所下降,而此时Prx4基因mRNA转录水平明显升高。转化细胞发展过程中呈现出细胞相对增殖率、迁移能力、集落形成能力整体逐渐升高的趋势;随着培养时间的增加,Prx4蛋白表达水平逐渐降低,Prx4基因m RNA转录水平无明显变化;但培养24 h时,恶性转化细胞mRNA基因转录水平显著高于正常胃黏膜细胞和胃腺癌细胞(P <0. 01)。结论正常胃黏膜细胞GES-1诱变16 h时已基本发生转化。细胞水平上,Prx4在转化过程中高表达,因此,Prx4主要参与并促进细胞转化过程。
关键词(KeyWords): 过氧化物酶-4;胃癌;细胞诱变;相关性
基金项目(Foundation):
作者(Authors): 邵明洋;杨静;贾茹涵;李文慧;石大林;韩跃武;
DOI: 10.13200/j.cnki.cjb.002724
参考文献(References):
- [1]WHO.All cancers(excluding non-melanoma skin cancer)estimated incidence,mortality and prevalence worldwide in 2012[EB/OL].(2017-09-02)[2018-07-31].http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx.
- [2]HERRERO R,PARK J Y,FORMAN D.The fight against gastric cancer-the IARC Working Group report[J].Best Pract Res Clin Gastroenterol,2014,28(6):1107-1114.
- [3]TEMPERO M A,MALAFA M P,BEHRMAN S W,et al.Pancreatic adenocarcinoma,version 2.2014:featured updates to the NCCN guidelines[J].J Natl Compr Canc Netw,2014,12(8):1083-1093.
- [4]WANG J,WANG X,YU F,et al.Combined detection of preoperative serum CEA,CA19-9 and CA242 improve prognostic prediction of surgically treated colorectal cancer patients[J].Int J Clin Exp Pathol,2015,8(11):14853-14863.
- [5]SISIK A,KAYA M,BAS G,et al.CEA and CA 19-9 are still valuable markers for the prognosis of colorectal and gastric cancer patien ts[J].Asian Pac J Cancer Prev,2013,14(7):4289-4294.(上接第898页)
- [6]TEMPERO M A,ARNOLETTI J P,BEHRMAN S,et al.Pancreatic adenocarcinoma[J].J Natl Compr Canc Netw,2010,8(9):972-1017.
- [7]TIAN S B,YU J C,KANG W M,et al.Combined detection of CEA,CA 19-9,CA 242 and CA 50 in the diagnosis and prognosis of resectable gastric cancer[J].Asian Pac J Cancer Prev,2014,15(15):6295-6300.
- [8]XU P,SHAO M Y,JIA R H,et al.Peroxiredoxin-4 as a potential biomarker of early gastric cancer screened by Cell-SE-LEX[J].Translat Cancer Res,2017,6(2):293-303.
- [9]SUN Z Q,YAN H M,JIA B,et al.Morphology and function of the malignant transformation of GES-1 of immortalized cell induced by MNNG[J].Chin J Modern Med,2012,22(22):14-18.(in Chinese)孙振卿,闫慧明,贾彬,等.从形态及功能研究MNNG诱变GES-1永生化细胞的恶性转化[J].中国现代医学杂志,2012,22(22):14-18.
- [10]CORSO C,JAMES M.Comparative genomic of N-methyl-N'-nitrosoguanidine-induced rat gastrointestinal tu-mors discloses a cytogenetic fingerprint[J].Environ Mol Muta-gen,2004,43(1):20.
- [11]HUANG Y F,SEFAH K,BAMRUNGSAP S,et al.Selective photothermal therapy for mixed cancer cells using aptamer-conjugated nanorods[J].Langmuir,2008,24(20):11860-11865.
- [12]GUO S L,ZHU S J,CHEN Q,et al.Effect of inhibition of potassium ions on the proliferation and migration of U-251 cells[J].J Chongqing Med Univ,2017,24(1):103-107.(in Chinese)郭玲,朱淑娟,陈清,等.格列本脲对U-251细胞增殖迁移的影响[J].重庆医科大学学报,2017,24(1):103-107.
- [13]PARK M H,JO M R,KIM Y R,et al.Roles of peroxiredoxins in cancer,neurodegenerative diseases and inflammatory diseases[J].Pharmacol&Ther,2016,163(4):1-23.
- [14]KIM T H,SONG J,ALCANTARA LLAGUNO S R,et al.Suppression of peroxiredoxin 4 in glioblastoma cells increases apoptosis and reduces tumor growth[J].Plos One,2012,7(8):e42818.
- [15]YI N,XIAO M B,NI W K,et al.High expression of peroxiredoxin 4 affects the survival time of colorectal cancer patients,but is not an independent unfavorable prognostic factor[J].Mol Clin Oncol,2014,2(5):767-772.
- [16]CHEN Y H,LI D R,HOU H X,et al.The effect on the results of MTT assay by different organic solvents and the color of drugs tested[J].J Guangxi Med Univ,2007,24(1):17-19.(in Chinese)陈艳华,黎丹戎,侯华新.不同溶剂和受试物颜色对MTT实验的影响[J].广西医科大学学报,2007,24(1):17-19.
- [17]ZHOU A R,ZHA X L,YAO L B,et al.Biochemistry and molecular biology[M].Beijing:People’s Medical Publishing House Co.,LTD,2013:312-355.(in Chinese)周爱儒,查锡良,药立波,等.生物化学与分子生物学[M].北京:人民卫生出版社,2013:312-355.收稿日期:编辑:王佳凤