| Background and objective: Gliomas are the most common primary intracranial tumor in the clinic.Because of the invasive growth characteristics of glioma cells,the mortality of glioma,especially high grade glioma,is still very high.It is urgent to put forward new methods for the treatment of glioma.Epithelial-Messenchymal Transition(EMT)plays an important role in the process of invasion and growth of glioma cells to surrounding tissues.EMT can enable glioma cells to obtain mesenchymal cell phenotype with high migration and invasion,at the same time,can obtain cancer stem cell specialty and treatment resistance.Therefore,research on EMT of glioma cells may provide a new direction for the treatment of gliomas.PDGF-D is a member of the PDGFs family.It has special biological functions and plays a role through combining with its receptor PDGFR-β.PDGF-D is expressed in a variety of tumor cells including glioma,which is related to the process of proliferation,invasion,and EMT of tumor cells,but the relationship between PDGF-D and EMT process of glioma cells is still unclear.Notch1 is one of the members of the Notch family,and the expression in glioma cells is positively correlated with the pathological grade of gliomas.HES1 is the downstream target of Notch1,Notch1/Hes1 signaling pathway is related to EMT occurrence of various tumor cells.Notch1 plays an important role in PDGF-D to promote tumor invasion and migration.However,the role of Notch1/Hes1 signaling pathway in PDGF-D promoting the invasion,migration and EMT of glioma cells has not been studied.The purpose of this study is to explore the relationship between PDGF-D and the migration,invasion and EMT process of glioma cells,and the role of Notch1/Hes1 signal pathway in this process.Methods: 1.Tumor tissue of glioma patients obtained by surgery were selected to conduct immunohistochemical experiments to verify the correlation between the expression of PDGF-D and its receptor PDGFR-β and the grade of gliomas.2.Cultivating glioma cells in vitro,knocking down PDGF-D with si RNA to verify the impact of low expression of PDGF-D on the migration,invasion,EMT process and Notch1/Hes1 signal pathway of glioma cells.3.Activating Notch1 in the low PDGF-D glioma cells to verify the role of Notch1 in the process of PDGF-D affecting the invasion,migration and EMT process of glioma cells and the change of Hes1 in this process.Results: 1.The results of immunohistochemicals showed that the average absorbance value of PDGF-D in glioma tissue was(8.209±5.688)%,and the average absorbance value of PDGFR-β was(7.829±5.688)%,both of which were higher than the average absorbance value of normal brain tissue(1.590±0.907)%,(1.717±1.257)%.They were positively correlated with the WHO classification of gliomas(rs=0.343,rs=0.450).2.Silencing the expression of PDGF-D can significantly inhibit the migration,invasion,EMT process,and Notch1/Hes1 signaling pathway of glioma cells..3.The activation of Notch1 in glioma cells reversed the influence of knocking down of PDGF-D on the invasion,migration,EMT process and expression of Hes1 of glioma.Conclusions: 1.The results of this study shows that the expression of PDGF-D and PDGFR-β in glioma tissue is higher than that in normal brain tissue,and it is positively correlated with the WHO classification of gliomas.2.The results of this study demonstrate that PDGF-D can promote the migration,invasion,and EMT processes of glioma cells,and this process can be regulated through the Notch1/Hes1 signaling pathway. |
PDF Full Text Request