全反式维甲酸通过PI3K/Akt通路参与睾丸畸胎瘤细胞生物学活性的机制研究  

Study on the mechanism of total trans-retinoic acid involved in the biological activity of testicular teratoma cells via PI3K/Akt pathway

作　　者：刁瑞英[1] 蔡学泳[1] 镇万华[1] 田芙颖[1] 甘辉梅[1] 赵丽 Diao Ruiying;Cai Xueyong;Zhen WanHua(Reproductive Centre, the second Hospital of shenzhen City, Shenzhen 518035, China)

机构地区：[1]深圳深圳市第二人民医院生殖医学科,广东518035 [2]东莞东莞市第三人民医院生殖医学中心,广东523326

出　　处：《国际泌尿系统杂志》2018年第3期382-386,共5页International Journal of Urology and Nephrology

基　　金：国家青年科学基金项目（81401258）;广东省自然科学基金（2014A030313652）;深圳市科创委基金（JCYJ20150330102401083）

摘　　要：目的 探讨全反式维甲酸（all-trans retinoic acid,ATRA）对人睾丸畸胎瘤NCCIT细胞的增殖、迁移和分化的影响及其相关分子机制.方法 选取人睾丸畸胎瘤细胞系NCCIT为研究对象.分别采用MTT和Transwell小室检测细胞的增殖和迁移变化;ELISA法检测细胞产生TGFβ1的变化;Western blot检测细胞内PI3K/Akt通路及其下游关键蛋白表达的影响.结果 ATRA显著抑制NCCIT细胞的增殖和迁移,并下调培养液上清中的TGFβ1;ATRA显著下调PI3K/Akt磷酸化及其下游蛋白Ecadherin、Occludin、MMP-2和-9的表达水平.而ATRA细胞核受体RXR和PI3K/Akt通路抑制剂,分别拮抗ATRA对NCCIT细胞增殖和迁移的抑制效应,并抑制ATRA对细胞的促分化作用.结论 ATRA参与抑制人睾丸畸胎瘤细胞的增殖和迁移并促进其分化,其机制可能是通过激活细胞核受体RXR进而调控PI3K/Akt通路来发挥作用的.Objective To investigate the effect of （all trans-retinoic acid,ATRA） on the proliferation,migration and differentiation of human testicular teratoma celline NCCIT and its related molecular mechanisms.Methods The human testicular teratoma cellline NCCIT was selected.MTT and Transwell assasys were used to detect the proliferation and migration of NCCIT cells.ELISA assay was used to detect the changes of TGF beta1 in cell culture supernatant.Western Blot was used to detect the expressions of Akt phosphorylation and PI3K/Akt pathway downstream proteins.Results ATRA significantly inhibited the proliferation and migration of NCCIT cells,and lowered the TGF beta1 levels in the cell culture supernatant.Furthermore,it significantly lowered the expression levels of Akt phosphorylation and downstream proteins Ecadherin,Occludin,MMP-2 and-9.However,both ATRA nuclear receptor RXR and PI3K/Akt pathwav inhibitors could antagonize the inhibitory effect of ATRA on the proliferation and migration of NCCIT cells and inhibit their differentiation to cells,respectively.Conclusions ATRA can inhibit the proliferation and migration of human testicular teratoma NCCIT cells and promote their differentiation.The mechanism may be mediated by activation of its nuclear receptor RXR through PI3K/Akt pathway.

关 键 词：睾丸肿瘤 畸胎瘤 维甲酸 

分 类 号：R737.21[医药卫生—肿瘤]