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The Effect Of Inhibit Proliferation Of Cancer Cell By Poly(AEP-g-PEI423)/pdcd4 Nano Micelles In Vitro And In Vivo

Posted on:2016-06-14Degree:MasterType:Thesis
Country:ChinaCandidate:M S HongFull Text:PDF
GTID:2334330470968608Subject:Pharmacy
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Objective:To evaluate the effect of inhibit proliferation of cancer call by delivery pdcd4 using poly(AEP-g-PEI423)in vitro and in vivo.Method:poly(AEP-PEI423)was synthesized by two steps.The poly(AEP-g-PEI423)/pdcd4 micelles were characterized,and the condensationand protection ability of pdcd4 by poly(AEP-g-PEI423)were confirmed by agarose gel electrophoresis assay.The cytotoxicity of poly(AEP-g-PEI423)on A549 and Hela cells were investigated by MTT assay.The expression of PDCD4?BAD?BAX in A549 and Hela cells were determined by Western Blotting assay.Furthermore,the therapeutic effects of poly(AEP-g-PEI423)/pdcd4 micelles were evaluated on xenografts nude mice.Results:poly(AEP-g-PEI423)and pdcd4 could form spherical micelles and the particle size is 182.9±3.6 nm.The cytotoxicity of poly(AEP-g-PEI423)was lower than that of PEI25K at the same polymer concentration of A549 and Hela cells.Compared with the pdcd4 group,the expression of PDCD4,BAD and BAX in A549 and Hela cells was significantly increased in poly(AEP-g-PEl423)/pdcd4 group.In vivo experiments,the poly(AEP-g-PEI423)/pdcd4 micelles could stably express the encoding protein PDCD4.That up-regulated the expression level of BAD and BAX,which promoted the cell apoptosis.Finally,the growth of xnograft tumor growth were inhibited.Conclusion:The results showed the cation polymer poly(AEP-g-PEI423)could efficiently delivered the pdcd4 in vitro and in vivo,therefore,inhibit the cancer cell proliferation.Which indicated the poly(AEP-g-PEI423)has promising application potential as gene carrier.
Keywords/Search Tags:poly(Aspartate-graft-PEI423), cationic polymer, pdcd4, xenograft tumor, gene expression
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