雷帕霉素、格尔德霉素联合用药对胃癌细胞sgc7901增殖及凋亡的影响

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1、雷帕霉素、格尔德霉素联合用药对胃癌细胞SGC．7901增殖及凋亡的影响中文摘要目的：证实雷帕霉素、格尔德霉素联合用药对胃癌细胞SGC．7901具有协同抑制作用，较雷帕霉素单独应用时抑制作用更强。方法：应用细胞培养技术培养人胃癌SGC．7901细胞，以MTT法检测两种药物对细胞的杀伤抑制作用；免疫细胞化学法检测胃癌细胞内P．Akt蛋白的表达情况；流式细胞仪检测胃癌细胞凋亡的变化情况。结果：两者联合用药对胃癌细胞具有协同作用，随雷帕霉素浓度增加呈剂量一时间双效应关系；免疫细胞化学方法检测显示，经格尔德霉素、雷帕霉素处理的SGC一7901细胞中p-Akt表达较单独用药时明显下降；流式细胞仪检测

2、显示，经格尔德霉素处理的SGC一7901细胞凋亡率增高(AnnexinV法)。结论：格尔德霉素可增强雷帕霉素对胃癌细胞SGC．7901的增殖抑制及诱导凋亡作用，其机制可能与格尔德霉素抑制了P13K通路的活化，即抑制了Akt的活化，从而使两者联合用药对胃癌细胞具有协同作用。关键词：格尔德霉素；雷帕霉素；胃癌细胞SGC．7901；增殖凋亡；P．AktEffectsofRapamycincombinedGeldanamycinOiltheProliferationandApoptosisinhumangastriccarcinomaSGC一7901Cells[abstract]Objectiv

3、e：ToConfirmthatthesynergisticinhibitoryeffectscombinationofRapamycinwithGeldanamyciningastriccancercellSGC一7901，whichhasastrongerinhibitationcomparedwithrapamycinalone．Methods：ThehumangastriccarcinomaSGC一7901celllinewasincubatedwithdifferentdruggroupsfordifferenttime，MTTassayforcellgrowthandviabi

4、lity，thecellapoptosisWasmeasuredbyflowcytometryusingannexinV／PI；immunocytochemistoryWastakentotesttheespressionofP-Akt．Results：MethylthiazoletetrazoliumanalysisshowedthatsynergisticinhibitionofcombinationofRapamycinwithGeldanamycin，theproliferationofcellsWasdepressedintimeandconcentration-depende

5、ntmanner；theexpressionofP—AktWasimproveddecreasedascomparedwitheithersubstancealoneshowedintheimmunocytochemistory．thecellapoptosispercentagewasincreasedobviouslydetectedbyflowcytometry．Conclusions：Geldanamycinimprovedgrowth·-inhibitoryandapoptosis--inductioneffectsofthemTORinhibitorrapamycininga

6、striccancercellSGC一7901byinhibitingtheactivationofP13KpathwaythatinhibitedtheactivationofAkt；thereforcombinationofthetwodrugshadasynergisticeffectingastriccancercells．Keywords：Geldanamycin；Rapamycin；gastriccancercellSGC一7901：proliferationandapoptosis；P-Akt4GARAPmTORHSP90DMSOPBSP13KAkt／PKBP．AktMTT

7、DABICCFBSODRPMSPSSgeldanamycinRapamycin缩略词表(Abbrevations)格尔德霉素雷帕霉素mammaliantargetofrapamycin哺乳动物雷帕霉素靶蛋白HeatShockProtein90热休克蛋白90dimethylsulfoxide二甲基亚砜phosphatebufferedsaline磷酸缓冲盐phosphoinositide一3kinase磷脂酰肌醇．3激酶protein