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Effects Of Celecoxib On Proliferation And Regulatory Networks Of Angiogenesis In Primary Acute Leukemia Cells

Posted on:2013-11-16Degree:MasterType:Thesis
Country:ChinaCandidate:X H GeFull Text:PDF
GTID:2234330362971456Subject:Internal Medicine
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Objective To evaluate cell proliferation effect of COX-2inhibitors celecoxib inprimary acute leukemia cell and investigate COX-2inhibitors celecoxib of anti-tumor,COX-2inhibitors celecoxib are used in acute leukemia prevention and treatment toprovide reliable experimental evidence.Methods16cases of collection of the Department of Hematology, FirstAffiliated Hospital of Henan University of Science and Technology in February2010toJuly2011with newly diagnosed untreated patients with acute leukemia,to take bonemarrow mononuclear cells isolated in routinely cultured in RPMI1640mediumcontaining the volume fraction of10%inactivated fetal bovine serum (FBS) with Ficolldensity gradient centrifugation method。 The Cells were treated with differentconcentrations (0~100μmol/L) of celecoxib,for prolifer ation effect of celecoxib onprimary acute leukemia cell with MTT assay, and the morphological change wereobserved under invert microscope,to explore the impact of celecoxib on the acuteleukemia cell proliferation.with mean comparison and multivariate analysis statisticalmethods。Results1. Acute leukemia cell growth inhibition rate increased from3.48%to53.24%by Celecoxib,and was time and dose dependent (P <0.05). With the drugaction and the extension of time, cell growth inhibition rate gradually increased.2. Untreated acute leukemia cells were round or oval, uniform size, vigorousgrowth, the suspension into a group was "grape-like" growth.But by80μmol/L of theplug past the cloth with the above cell co-culture after48h, can be observed to celecoxibcloth apparent toxic effects on cells, smaller cell size, deformation, cell membraneintegrity, but the foam phenomenon,particles increased in cells, cell debris increasedsignificantly.Conclusion Celecoxib significantly inhibites the proliferation of acute leukemia cells, and enables acute leukemia cells morphology changes, leading to celldegeneration and necrosis, and ultimately in the death of leukemia cells. Therefore,celecoxib may become a new drug to treat leukemia, but the specific mechanismremains to be further research. Objective In order to further investigate the proliferation which was inhibitedby celecoxib in acute leukemia cells,and to explore the occurrence and developmentof angiogenesis network control system in leukemia.Methods16cases of collection of the Department of Hematology, FirstAffiliated Hospital of Henan University of Science and Technology in February2010toJuly2011with newly diagnosed untreated patients with acute leukemia,to take bonemarrow mononuclear cells isolated in routinely cultured in RPMI1640mediumcontaining the volume fraction of10%inactivated fetal bovine serum (FBS) with Ficolldensity gradient centrifugation method. After taking the logarithmic growth phase cells,divided into two groups, the control group by adding Celebrex0μmol/L, and theexperimental group by adding80μmol/L, both cultured for48hours.immunocytochemistry was used to detect expression of VEGF、bFGF、TGF-β inprimary acute leukemia cell. Measurement data were compared using the t test, analysisof variance, linear correlation analysis and other statistical methods to explore celecoxibcloth of acute leukemia angiogenesis regulatory networks.Results1.The control group (0μmol/L celecoxib) of the positive expressionrate of VEGF,、bFGF,、TGF-β were46.69±7.12,27.19±8.19,79.19±16.23,Points, respectively,102.63±12.97,56.81±14.91,161.56±36.20, the experimentalgroup (80μmol/L celecoxib) of the positive expression rate of VEGF, bFGF, TGF-βwere36.19±5.99,16.38±5.07,81.05±15.76,points, respectively,73.38±11.02,36.31±9.62,165.44±33.77。VEGF, bFGF of the experimental group was significantlyhigher (P <0.01) and the difference was statistically significant. But TGF-β in theexperimental group and control group were not statistically significant (P>0.05).2. In order to explore the expression of VEGF, bFGF,TGF-β in acute leukemiacells,whether there is correlation, we use correlation analysis and the results show that the expression of VEGF,bFGF, TGF-β was positively correlated (r=0.534,0.408, P<0.01).Conclusion Celecoxib can effectively inhibit acute leukemia cell which cansecret of VEGF, bFGF, TGF-β,and there is a positive correlation between VEGF,bFGF,and TGF-β, which indicate their common participation in the network controlsystem of leukemia angiogenesis. Therefore, this study show that celecoxib can inhibitthe growth and proliferation of leukemia cells by inhibiting of leukemia angiogenesis.At the same time, as a target for VEGF, bFGF, TGF-β anti-angiogenesis therapy whichwill be expected to become a new treatment of leukemia patients.
Keywords/Search Tags:Acute leukemia, the COX-2inhibitors, celecoxibCelecoxib, acute leukemia, angiogenesis, VEGF, bFGF, TGF-β
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