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Down-Regulation of AP-4 Inhibits Proliferation, Induces Cell Cycle Arrest and Promotes Apoptosis in Human Gastric Cancer Cells 英文参考文献.docVIP

Down-Regulation of AP-4 Inhibits Proliferation, Induces Cell Cycle Arrest and Promotes Apoptosis in Human Gastric Cancer Cells 英文参考文献.doc

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Down-Regulation of AP-4 Inhibits Proliferation, Induces Cell Cycle Arrest and Promotes Apoptosis in Human Gastric Cancer Cells 英文参考文献

Down-RegulationofAP-4InhibitsProliferation,Induces CellCycleArrestandPromotesApoptosisinHuman GastricCancerCells XinghuaLiu1.,BoZhang1.,YanGuo2,QiLiang1,ChangyaoWu1,LeiWu1,KaixiongTao1, GuobinWang1*,JianyingChen1* 1DepartmentofGeneralSurgery,UnionHospital,TongjiMedicalCollege,HuazhongUniversityofScienceandTechnology,Wuhan,China,2DepartmentofMaternaland ChildHealth,SchoolofPublicHealth,TongjiMedicalCollege,HuazhongUniversityofScienceandTechnology,Wuhan,China Abstract Background: AP-4 belongs to the basic helix-loop-helix leucine-zipper subgroup; it controls target gene expression, regulates growth, development and cell apoptosis and has been implicated in tumorigenesis. Our previous studies indicatedthatAP-4wasfrequentlyoverexpressedingastriccancersandmaybeassociatedwiththepoorprognosis.The purposeofthisstudyistoexaminewhethersilencingofAP-4canalterbiologicalcharacteristicsofgastriccancercells. Methods:TwospecificsiRNAstargetingAP-4weredesigned,synthesized,andtransfectedintogastriccancercelllinesand human normal mucosa cells. AP-4 expression was measured with real-time quantitative PCR and Western blot. Cell proliferationandchemo-sensitivityweredetectedbyCCK-8assay.Cellcycleassayandapoptosisassaywereperformedby flowcytometer,andrelativeexpressionofcellcycleregulatorsweredetectedbyreal-timequantitativePCRandWestern blot,expressionofthefactorsinvolvedintheapoptosispathwaywereexaminedinmRNAandproteinlevel. Results:TheexpressionofAP-4wassilencedbythesiRNAstransfectionandtheeffectsofAP-4knockdownlasted24to 96hrs.ThesiRNA-mediatedsilencingofAP-4suppressedthecellularproliferation,inducedapoptosisandsensitizedcancer cells to anticancer drugs. In addition, the expression level of p21, p53 and Caspase-9 were increased when AP-4 was knockdown,buttheexpressionofcyclinD1,Bcl-2andBcl-xLwasinhibited.Itdidn’tinducecellcyclearrestwhenAP-4was knockdowninp53defectgastriccancercelllineKato-III. Conclusions: These results illustrated that gene silencing of AP-4 can efficiently inhibited

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