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The Effect Of Nutlin-3α Induced P73aon The Cell Cycle Arrest Of Colon Cancer Cell And The Mechanism Of This Effect

Posted on:2014-08-29Degree:MasterType:Thesis
Country:ChinaCandidate:L WangFull Text:PDF
GTID:2254330425458362Subject:Pathology and pathophysiology
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Purpose: This project is to search for a suctable Nutlin-3a concentration whichcauses cancer cell to senescence but not to quiescence. That provided experimentalbasis for p53mutations and p53null colon cancer which treated by Nutlin-3a andreducing the possibility to the carcinoma recurrence.Methods:Caco-2,p53mutations but contents mt-p73α was first acclimated inDMEM containing10%fetal bovine serum for24h before exposure to Nutlin-3. wetreatred Caco-2cell with0μM、2.5μM、5μM、10μM、20μM、40μM、60μM and80μMof Nutlin-3a.Then tested the inhibitory effects of Nutlin-3a on cell lines Caco-2by MTT assay,tested p73α experience of the treated Caco-2cells by western blottingand demonstrated the senescence cell by SA-beta gal dyeing to analysis with coloncancer cell after72hours. We searched for a concentration range of Nutlin-3a.Nutlin-3a could cause cancer cell to death and senescence but not quiescence at theseconcentration. So that,the possibility of cancer recurrece could be reduced afterremoving chemotherapy drugs. Meanwhile, we explored the effective mechanism ofNutlin-3a.Results:Nutlin-3a can restrain the growth of Caco-2cell; Nutlin-3a can raise theexpression of p73α in Caco-2cell,this effect is Nutlin-3a concentration dependent;The stationary optimal concentration range of Nutlin-3a which causes colon cancer tosenescence, but not quiescence is5-10μM.Conclusions:Nutlin-3a can enhance the expression of p73α in Caco–2cell andthis effect is Nutlin-3a concentration dependent. The stationary optimal concentrationrange of Nutlin-3a is5-10μM. At these concentrations, the anti-tumor effect ofNutlin-3a is the best.
Keywords/Search Tags:colon cancer, Nutlin-3a, p73α, cell senescence, cell quiescence
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