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Study On Relationship Between Reversal Of Multidrug Resistance Of Oral Carcinoma Cells KBV200 And Angiogenesis By (-)-epigallocatechin-3-gallate

Posted on:2008-03-29Degree:MasterType:Thesis
Country:ChinaCandidate:L LiFull Text:PDF
GTID:2144360218456441Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
Objective:To investigate the effect of EGCG administrated with chemical on experimental chemotherapy against xenografts derived from human oral epidermoid carcinoma KBV200 and its effects on angiogenesis,VEGF and HIF-1α,and to explore the mechanism.Methods:The antiangiogenesis effect in vivo of EGCG on CAM assay was observed.The models of drug-sensitive KB and KBV200 xenograft in nude mice were established and received VCR and EGCG of desired drug and dosage for two weeks.Observated angiogenesis of the xenograft tumor by HE stain.The expression of VEGF,CD34 in tumor tissues of each group were detected by immunohistochemistry and calculated the difference of MVD.The apoptosis of KBV200 cells was observed with TUNUL.Quantitative ELISA for serum VEGF was performed according to manufacturer's recommendations.The mRNA expressi on level of VEGF,HIF-1αwere detected by RT-PCR assay accordingly.Resuits:80~320mg·L-1EGCG inhibit the angiogenesis of CAM.Tumor inhibition was observed in the KBV200 xenografts following a 14-day treatment withl0,20and40 mg·kg-1of EGCG combined with VCR,with total growth inhibition of 69.1%,72.8%,76.1%,respectively(P<0.01).The angiogenesis was less in the combination groups.MVD were lower of the three co-adminis tration groups than that of VCR group(P<0.05).The rate of cell apoptosis exhibiting as VE low group:45.1%,VE mid group:52.3%,VE high group:58.1% respectively,were higher than that ofVCR group(32.5%)(P<0.05).The combinat ion groups of EGCG at midst,high dose inhibited mRNA and protein expression of VEGF.All the combination groups of EGCG at low,midst,high dose inhibited mRNA expression of HIF-1αin KBV200 xenografted models significantly.Conclusion:The mechanism of overcoming KBV200 MDR of EGCG is probably associated with inhibit the angiogenesis of tumor by decrease the expression of HIF-1α,VEGF to enhance synergic anti-cancer action of VCR.
Keywords/Search Tags:catechin, reversal agents, oral carcinoma, multidrug resistance, HIF-1α, VEGF
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