DADS负调控uPAR/uPA信号抑制人结肠癌SW480细胞侵袭和EMT  

DADS inhibits human colorectal cancer SW480 cell invasion and EMT by negatively regulating uPA/uPAR signaling pathway

作　　者：谭拓 夏红 苏坚 杨晶 刘芳 苏波 苏琦 TAN Tuo;XIA Hong;SU Jian;YANG Jing;LIU Fang;SU Bo;SU Qi(Institute of Cancer Research,Hunan Provincial Key Laboratory of Cancer Cell and Molecular Pathology,Hengyang 421001,Hunan,China;Department of Pathology,the Second Affiliated Hospital,Hengyang 421001,Hunan,China;Institute of Pharmacy and Pharmacology,Key Laboratory for Pharmacoproteomics of Hunan Provincial University,Hengyang Medical School,University of South China,Hengyang 421001,Hunan,China;Department of Oncology,Changsha Wangcheng District People's Hospital,Changsha 410200,Hunan,China)

机构地区：[1]南华大学衡阳医学院肿瘤研究所,湖南省肿瘤细胞与分子病理学重点实验室,湖南衡阳421001 [2]南华大学衡阳医学院附属第二医院病理科,湖南衡阳421001 [3]南华大学衡阳医学院药学与药理学研究所,湖南省高校药物蛋白质组学重点实验室,湖南衡阳421001 [4]长沙市望城区人民医院肿瘤科,湖南长沙410200

出　　处：《中南医学科学杂志》2024年第5期689-694,704,共7页Medical Science Journal of Central South China

基　　金：国家自然科学基金项目(81973532)。

摘　　要：目的探讨二烯丙基二硫(DADS)抑制人结肠癌SW480细胞侵袭和上皮间质转化(EMT)的可能机制。方法免疫组化检测结肠癌组织中尿激酶型纤溶酶原激活剂(uPA)受体(uPAR)的表达。基因转染技术构建uPAR过表达细胞。实验分为SW480组、SW480+DADS组、uPAR组、uPAR+DADS组。迁移、侵袭实检测各组细胞迁移与侵袭能力。RT-PCR、Western blotting分别检测相关信号通路分子mRAN及其蛋白的表达。裸鼠实验验证DADS对uPAR过表达SW480细胞移植瘤的影响。结果结肠癌组织中uPAR表达显著高于癌旁正常黏膜组织(P<0.05)。成功构建稳定uPAR过表达SW480细胞。uPAR过表达上调uPA、uPAR表达,而DADS下调uPA、uPAR表达。uPAR过表达增强细胞迁移、侵袭能力,DADS抑制uPAR过表达细胞的迁移、侵袭能力。DADS通过下调Vimentin、基质金属蛋白酶(MMP-9)表达,上调E-cadherin、组织金属蛋白酶抑制物(TIMP)-3表达抑制SW480细胞EMT。裸鼠实验结果显示,DADS可体内抑制uPAR过表达SW480细胞EMT。结论DADS通过负调控uPAR/uPA信号体内外抑制人结肠癌SW480细胞侵袭和EMT。Aim To explore the possible mechanism of diallyl disulfide(DADS)to inhibit invasion and epithelial-mesenchymal transition(EMT)of human colorectal cancer SW480 cells.Methods The expression of urokinase-type plasminogen activator(uPA)receptor(uPAR)in colon cancer tissues was detected by immunohistochemistry.uPAR overexpressing cells were constructed by gene transfection.The experiment was divided into SW480 group,SW480+DADS group,uPAR group,uPAR+DADS group.The cell migration and invasion ability in each group were detected through migration and invasion tests.The expression of mRAN and its protein in related signaling pathways was detected by RT-PCR and Western blotting.Nude mouse experiments were conducted to verify the effect of DADS on uPAR overexpressing SW480 cell transplantation tumors.Results The expression of uPAR in colon cancer tissues was significantly higher than that in adjacent normal tissues(P<0.05).SW480 cells with stable overexpression uPAR were constructed successfully.Overexpression of uPAR up-regulated the expression of uPA and uPAR,while DADS down-regulated the expression of uPA and uPAR.uPAR overexpression enhanced cell migration and invasion,whereas DADS inhibited the migration and invasion of uPAR-overexpression cells.DADS inhibited EMT in SW480 cells by down-regulating the expression of Vimentin and matrix metalloprotein(MMP)-9,and up-regulating the expression of E-cadherin and tissue inhibitor of metalloproteinase(TIMP)-3.The results of nude mouse experiments showed that DADS can inhibit uPAR overexpression in SW480 cells and EMT in vivo.Conclusion DADS inhibits human colon cancer SW480 cell invasion and EMT by negatively regulating uPAR/uPA signaling pathway in vivo and in vitro.

关 键 词：二烯丙基二硫 人结肠癌细胞 uPAR/uPA信号 侵袭 EMT 体内外 

分 类 号：R735.35[医药卫生—肿瘤]