CDDP获得侵袭转移能力的分子机制-论文.pdf

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1、·1670·A549／CDDP人肺腺癌耐顺铂细胞A549／CDDP获得侵袭转移能力的分子机制陈新来，胡惠军，潘勇权，邹伟文，周文泉，古彩红，王昊Molecularmechanism0facquisition0finvasionandmetastasisphenotypeinhumanlungcancercelIlineA549／CDDPChenXinlai，HuHuijun，PanYongquan，ZouWeiwen，ZhouWenquan，GuCaihong，WangHao。PathologyDepar

2、tment。eThirdPeople'sHospitalofHuizhou，GuangdongHu~hou516002，China；2DepartmentofMicrobialandBio—chemicalPharmacy．SchoolofPharmaceuticalSciences，SunYat—senUniversity，GuangdongGuangzhou510006，China．【Abstract】Objective：Toinvestigatethemolecularmechanismofacqu

3、isitionofinvasiveandmigratoryphenotypeofcisDlatin—resistanthumanlungcancercelllineA549／CDDP．Methods：ThecapabilityofmigrationandinvasionofA549ce11sandA549／CDDPceilsandtheefectofLY294002onmigrationandinvasionofA549／CDDPcellsweredetectedbvWOundhealingassayan

4、dtranswellinvasionassay．WesternblottingwasusedtodetecttheactivationofAKT，NF—KBandSTAT3signalingpathway．ThesensibilityofA549cellsandA549／CDDPceHstocisplatinandtheeffectofLY294002onsensibilityofA549／CDDPcellstocisplatinwasmeasuredbyMTTassay．Results：Compared

5、toA549cells，theresistanceofA549／CDDPcellstocisplatinandthemigrationandinvasionweresignificantlyen—hanced．TheresultsofwesternblottingdemonstratedthatAKTsignalingpathwayisactivated，butnotNF—KBandSTAT3signalingpathways．LY294002suppressedmigrationandinvasiono

6、fA549／CDDPcellsandenhancedthesen—sibilityofA549／CDDPcellstocisplatin．Conclusion：AcquisitionofinvasiveandmigratoryphenotypeofhumanlungcelllineA549／CDDPislinkedwithactivationofPI3K／AKTsignalingpathway．【Keywor~lA549／CDDP；migrationandinvasion；drugresistance；P

7、I3K／AKT；LY294002ModernOncology2013，21(08)：1670—1674【摘要】目的：研究人肺腺癌耐顺铂细胞A549／CDDP获得侵袭转移能力的分子机制。方法：细胞划痕实验和Transwell侵袭实验比较A549和A549／CDDP的转移侵袭能力的差别，以及LY294002对A549／CDDP侵袭转移能力的影响。蛋白质免疫印迹技术检测AKT，NF—KB，STAT3信号通路的激活情况，MTr法检测A549和A549／CDDP对顺铂的敏感性，以及PI3K／AKT通路抑制剂LY29

8、4002对A549／CDDP细胞对顺铂的敏感性的影响。结果：A549／CDDP对顺铂的耐药性以及侵袭转移能力相对于A549有明显增强。Westernblot结果表明：A549／CDDP细胞AKT通路被激活，NF—KB，STAT3通路没有明显变化。LY294002能够明显抑制A549／CDDP的侵袭转移能力并且能够提高A549／CDDP对于顺铂的敏感性。结论：A549／CDDP细胞相对于A549细胞的侵袭转移能力明显增强，其机制