hrgerbb信号系统与22rv1前列腺癌细胞增殖关系研究-study on the relationship between hrg erbb signal system and proliferation of 22rv 1 prostate cancer cells.docx

中文摘要HRG/ErbB信号系统与22RV1前列腺癌细胞增殖关系研究目的：探讨HRG/ErbB信号系统对激素非依赖性前列腺癌细胞株22RV1增殖的影响及其作用机制。方法：首先，应用共聚焦显微镜和流式细胞仪技术对22RV1前列腺癌细胞HER-2和HER-3的表达进行定性和定量的检测；其次，应用MTT法明确HRG对22RV1前列腺癌细胞增殖的影响；最后，结合流式细胞仪周期检测及蛋白印记技术明确HRG/ErbB信号系统影响22RV1前列腺癌细胞增殖的具体作用机制。结果：1、共聚焦显微镜技术证实FITC标记的HER2和PE标记的HER3在前列腺癌细胞株22RV1都有低度表达。2、FITC-HER2表达率﹦（6.4800±2.39729）%，PE-HER3表达率﹦（4.6200±1.33492）%，表明HER2、HER3在22RV1前列腺癌细胞均低表达。3、MTT实验表明HRGβ1能促进22RV1细胞增殖。4、HRGβ1激活22RV1前列腺癌细胞PI3K/AKT信号通路，p-AKT的表达显著升高。5、随着HRGβ1干预时间的延长，S期细胞比例逐渐升高，G0/G1期细胞比例逐渐降低。6、随着HRGβ1干预时间的延长，cyclinD1表达量随之增加。结合流式细胞仪检测的细胞周期改变，HRGβ1可能通过诱导cyclinD1表达升高从而促进G0/G1期向S期转换。7、HRGβ1通过降解IκB快速活化NF-κB通路。结论：HRG/ErbB信号系统促进22RV1前列腺癌细胞增殖，其机制涉及PI3K/AKT通路活化和cyclinD1的表达升高，同时伴有NF-κB通路的激活。关键词：HRG/ErbB信号系统，激素非依赖性前列腺癌，22RV1细胞株，PI3K/AKT通路，细胞周期，NF-κB1ABSTRACTROLEOFHRG/ErbBSIGNALSYSTEMINTHEPROLIFERATIONOF22RV1PROSTATECANCERCELLLINEObjective：Investigatingthemechanismofprolilferationof22RV1cellinductedbythesignalofHRG/ErbBsystem.Methods:First,detectingtheexpressionofHER-2andHER-3bytheconfocalmicroscopyandflowcytometry;Secend,usingthemethordsofMTTassaytoexaminingtheinfluenceofHRGon22RV1cellprolilferation;Third,usingthetechnologyofflowcytometryandwesternblottoinvestigatethemechanismofprolilferationof22RV1cellinductedbytheHRG/ErbBsignalsystem.Results:1.TheFITCconjugatedHER2andPEconjugatedHER3arelowlevelespressedon22RV1cells.2.FITC-HER2%﹦（6.4800±2.39729）%，PE-HER3%﹦（4.6200±1.33492）%.3.HRGβ1promtotetheproliferationprocessof22RV1cells.4.HRGβ1activatthepasswayofPI3K/AKT.5.UndertheinterfereofHRGβ1,thecellPercentageofSphasebecomeincreasedfollowedbythedecreaseofG0/G1phasescellPercentage.6.WiththeprolongoftheHRGβ1intervention,italsohappenstheincreasingresultofcyclinD1expression.7.HRGβ1canactiveNF-κBpasswayinaquicklymanner.Conclusion:TheHRG/ErbBsignalsystemcanpromtotetheproliferationprocessof22RV1prostatecancercells,themechanisminvolvesinisactivatingofthePI3K/AKTpasswayandtheincreasingexpressionofcyclinD1alsowiththeactivatingofNF-κBpassway.KeyWords:HRG/ErbBsignalsystem,AndrogenIndependentProstateC