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Expression Of FABP5 And Preliminary Study On Its Function And Its Relationship With Sensitivity To All-Trans Retinoic Acid In Glioma

Posted on:2018-10-27Degree:MasterType:Thesis
Country:ChinaCandidate:W W GaoFull Text:PDF
GTID:2334330515452886Subject:Pathology and pathophysiology
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Objective Different glioma cell lines response differently to all-trans retinoic acid(ATRA)treatment.Fatty acid-binding protein 5(FABP5)is supposed to be related with ATRA sensitivities of cancer cells for its possibly mediating growth-promoting signaling.In addition,FABP5 is also involved in metastasis in some cancers.However,the role of FABP5 in glioma remains unclear.Here,we intended to investigate the expression of FABP5 protein in glioma of different grades,the role of FABP5 in RA sensitivity and the molecular function of FABP5 in the carcinogenesis and metastasis of glioma.So as to provide a new idea for further study of FABP5-related targeted therapy in glioma.Methods1)We examined FABP5 expression patterns of 137 astrocytoma tissues and 23 paracancerous brain tissues using immunohistochemistry staining.The relationship between FABP5 expression and clinic pathological parameters was statistical analysised.According to the clinical follow-up data,we draw survival curve.2)Human glioma cell lines(U251/A172/T98G)were cultured in vitro,the expression of FABP5 protein in three glioma cell lines was detected by Western blotting;To investigate the effect of FABP5 gene on the proliferation,invasion and metastasis of glioma cells,FABP5 protein in A172 and T98 G cells was down-regulated by si RNA.The cell viability,migration and invasion were detected by MTT assay,scratch test and Transwell respectively.3)Cells were treated with different concentrations of ATRA(1,5,10μM).HE staining was performed to observe the morphological changes of glioma cells;the effect of ATEA on the proliferation of glioma cells was detected by MTT assay;the expression of FABP5 protein was detected by Western blotting and immunocytochemistry before and after ATRA treatment in glioma cells.Results1)The expression of FABP5 was significantly higher in glioma than that in normal control(P<0.05),and positively correlated with the histological grade and poor prognosis in glioma(P<0.05).2)FABP5 is expressed in the U251/A172/T98 G cell lines,which is shown to increase sequentially.Downregulation FABP5 expression in glioblastoma cells(A172,T98G)successfully inhibited cell proliferation rates,migration and invasion.3)There were no significant differences in the morphology of the three cells before and after ATRA treatment.Treatment of A172,T98 G,U251 cells lines with 1,5 or 10 mM ATRA all failed to suppress their growth expect A172 to 10mM ATRA at 48 h.However,the level and distribution of FABP5 expression were not altered after RA treatment.Conclusion FABP5 signi?cantly promotes glioblastoma cells growth and metastatic potential,and FABP5 is an important determinant of clinical outcome in glioma patients.Glioblastoma cell lines were less sensitive to ATRA and had no significant association with FABP5.
Keywords/Search Tags:brain tumor, glioma, all-trans retinoic acid, FABP5, glioma cells
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