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Enhancement Of Ovary Cancer Cells’Sensitivity To Taxol By Aurora Kinase Inhibitor VX680

Posted on:2014-07-31Degree:MasterType:Thesis
Country:ChinaCandidate:X JinFull Text:PDF
GTID:2254330422964455Subject:Obstetrics and gynecology
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Objective observe the Aurora kinase inhibitor VX680’s influence on cancercells’ proliferation and apoptosis and explore the mechanism of its effects;completea preliminary inquiry of VX680and Taxol’s combined application in ovary cancercellsMeyhods take the CCK8method to investigate VX680’s inhibition effect oncell proliferation;FCSA method to analysis cell cycle arrest and apoptosis caused byVX680alone or combined with Taxol,western blot to determine protein-expresslevel varying with the concentration of VX680Results VX680inhibit cancer cells’ proliferation the CCK8results implythat in contrast with control, the experimental group shows a significant inhibition ofproliferation increasing with the concentration of VX680:in Hela, with theconcentration of VX680increases from100nM to1μM,the72h inhibition ratio risesby17.1%(from13.7%to30.8%).The results of FCSA show that inhibition of Aurorakinases with VX680induces apoptosis and endoreduplication in Hela.Under theFluorescence microscope, we observed complex variation of the nucleus, includingkaryopyknosis, karyorrhexis, amplification of nucleus and a dramatic decrease intotal number of cells since the concentration of100nM. FCSA resultsdemonstrate a increasing number of cells containing8N chromosome with VX680impact on Hela for48h.The result of western blot reveals that VX680effectivelyinhibits Aurora kinases’ expression. Coincide with the down regulation of Aurorakinases, the expression level of protein PARP, cleaved-caspase-3increases obviously.In ovary cancer cells, within a special range of concentration, VX680enhances theinhibition of proliferation and apoptosis induced by Taxol. Conclusion Aurora kinase inhibitor VX680can effectively down regulatethe expression of Aurora kinases in cancer cells, resulting with cells’ proliferationinhibition and apoptosis.Aurora kinase inhibitor VX680and Taxol generate asynergistic effect in inducing ovary cancer cells’ apoptosis.
Keywords/Search Tags:VX680, Taxol, Aurora kinase, cell cycle arrest, cell apoptosis
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