地西他滨诱导miR-200c/141表达抑制肾癌细胞侵袭迁移  

Decitabine Inhibit Invasion and Migration Ability of Renal Cell Carcinoma Cells by Up-regulating MiR-200c/141

作　　者：陈梦娇 王华[2] 陈锦超[2] 赵安[2] 胡海红 曾苏 CHEN Mengjiao;WANG Hua;CHEN Jinchao;ZHAO An;HU Haihong;ZENG Su(College of Pharmaceutical Sciences,Zhejiang Province Key Laboratory of Anti-Cancer Drug Research,Zhejiang University,Hangzhou 310058,China;Cancer Hospital of Zhejiang Province,Hangzhou 310022,China)

机构地区：[1]浙江大学药学院,浙江省抗肿瘤药物临床前研究重点实验室,杭州310058 [2]浙江省肿瘤医院,杭州310022

出　　处：《中国现代应用药学》2019年第13期1601-1607,共7页Chinese Journal of Modern Applied Pharmacy

基　　金：国家重点研发计划(2017YFC0908600);国家自然科学基金项目(81773817)

摘　　要：目的探讨DNA甲基转移酶抑制剂地西他滨对人肾细胞癌786-O和769-P细胞侵袭迁移能力的影响,并进行相关机制的研究。方法实时荧光定量PCR法检测肾癌及其癌旁组织中miR-200c/141的表达量及2.5μmol·L^-1地西他滨对肾癌细胞系miR-200c/141的诱导作用;Transwell试验、划痕试验分别检测地西他滨、miR-200c/141对细胞侵袭迁移的影响;实时荧光定量PCR法、蛋白印迹法检测786-O和769-P细胞系钙黏蛋白表达量。结果与正常肾癌旁组织相比,miR-200c/141在肾癌组织中的表达量显著下调。2.5μmol·L^-1地西他滨能诱导786-O和769-P细胞系中miR-200c/141的表达增加。地西他滨、miR-200c/141均能抑制细胞的侵袭迁移能力。786-O和769-P细胞经地西他滨处理后,与上皮间充质转化相关的钙黏蛋白表达水平显著上调。结论地西他滨可以通过上调miR-200c/141的表达水平减弱肾癌细胞系的侵袭迁移能力。OBJECTIVE To investigate the effect and mechanism of DNA methyltransferase inhibitor decitabine on the invasion and migration ability of renal cancer cells 786-O and 769-P.METHODS The miR-200c/141 expression levels in renal cell carcinoma and its adjacent tissues were detected by RT-qPCR.MiR-200c/141 were induced by 2.5 μmol·L^-1 decitabine and detected by RT-qPCR.Transwell assay and scratch assay were used to detect the effect of decitabine,miR-200c/141 on cell invasion and migration respectively.The mRNA and protein levels of E-cadherin were detected by RT-qPCR and Western blot. RESULTS Compared with adjacent tissues,miR-200c/141 were significantly down regulated in renal cell carcinoma.The expression of miR-200c/141 could be induced in the 786-O and 769-P cells after treated with 2.5 μmol·L^-1 decitabine.Scratch assay and Transwell assay results showed that decitabine,miR-200c/141 could inhibit cell migration and invasion.The expression of E-cadherin was upregulated in 786-O and 769-P cells after treated with decitabine,which associated with epithelial mesenchymal transition.CONCLUSION Decitabine can weaken the migration and invasion ability of 786-O and 769-P cells by up-regulating the expression of miR-200c/141.

关 键 词：地西他滨 MIR-200C miR-141 肾细胞癌 侵袭迁移 

分 类 号：R965.1[医药卫生—药理学]