Hippo信号通路介导PTEN调节PI3KAKTmTOR信号通路影响肝癌细胞增殖能力精品.pdf

Hippo信号通路介导PTEN调节PI3K/AKT/mTOR信号通路影响肝癌细胞增殖能力徐瑞2,李丽娜2,王文娟2*(2陕西省肿瘤医院内一科，西安712061；2西安交通大学第一附属医院肿瘤内科；■■通讯作者，E-mail：[e-mail])摘要：目的研究Hippo信号通路下游效应分子YAP在肝细胞肝癌中的作用及其机制。方法在肝癌细胞系BEL7702和HepG2中外源性过表达和沉默YAP,利用细胞计数及裸鼠成瘤的方法检测YAP对肝癌细胞体内体外增殖能力的影响。通过Westernblot检测过表达和干扰YAP后PTEN及PI3DAKT/mT0R信号通路相关蛋白的改变。在过表达YAP蛋白的肝癌细胞中分别给予雷帕霉素或过表达PTEN,检测肝癌细胞体内体外增殖能力改变。免疫共沉淀检测YAP与PTEN蛋白的体内结合。结果过表达YAP可以增强肝癌细胞体内体外增殖能力(P<6.65)，干扰YAP则岀现相反情况。PTEN过表达或给予PI3K/AKT/mT0R信号通路的抑制剂雷帕霉素(npanyyp)，均能够抑制YAP过表达带来的肝癌细胞增殖和成瘤能力的增加(P<6.65),YAP蛋白与PTEN蛋白在肝癌细胞HepG2中存在体内结合。结论Hippo信号通路可以介导PTEN通过PI3K/AKT/mT0R信号通路促进肝细胞肝癌细胞增殖和成瘤。关键词：Hippo信号通路；PTEN；PI3KAKT/mT0R信号通路；肝细胞肝癌；细胞增殖中图分类号：R735.7文献标志码：A文章编号：1027-6611(2222)12-1277-27DO3：12.13753/j.Pc627-6611.2222.12.021HippopathwayaffectscellproliferationofhepatocellularcarcinomabyregulatingP3K/AKT/mTORpathwayvipPTENXURui1，LILica1，WANGWeejuac2*(1DepartmentofInternalMedicine，ShaanxiProvinceCancerHospital，Xi'an710061,China；2DepartmentfMedialOncolofy，FirstAffiliatedHospitalfXi，aaJiaotongUniversity；^Correspondingaahor,E-mait,[e-mail])Abstraci:ObjectiveTostudytheroloofthedownstreameffectorYAPofHipposipnaCn)patewayichepatocerUancarcicogeresisanditsmechanism.MetOoftTheeffectsofYAPontheproliferatiocOnnitroandincieweredetectePbycePcountendcudcmoosetumonformationinheeatocellulyecacceocellsBEL7402andHepG2afteoYAPoverexpressioconYAPintenerecco.WesternbloiwasusedtodetecttheexpressioooftheproteicsrelateetoPI3K/AKT/mT0RsipcalincpathwnyphepatocellulaocacceecellswithYAPoverexpressioooeYAPintenerepce.TheproliferatiooinnitroandincCcwnsdetectedpYAP-overexpressioocellswhichweretreateewithPTENoverexpressioooerapamycic,aninhibitorofPI3K/AKT/mT0Rsipdalincpathway.ImmudoprecipitatioownsusedtoyetectthebindincofYAPandPETNproteininic.ResuOtOverexpressionofYAPephadceXtheproliferatiodofBEL7462andHepG2invitroandinvivo(P<2.25)，whiletheinterferexcewithYAPhadtheoppositeeffechRapamycicoePTEN-overexpressiooindiPiteXtheidcreasesofproliferaCopandtumoripexesisinhepatocePUaecadceecellscausedbyYAPoverexpressioo(