The Study On The Effect Of DLL4 On Radiosensitivity Of Non-small Cell Lung Cancer And Its Mechanism

Background: Tumor radiation resistance is the key factor leading to poor prognosis,so improving radiosensitivity and reducing the damage of surrounding normal tissue is the focus of the current research.The purpose of this study is to detect the expression level of DLL4 in non-small cell lung cancer and to explore the radiosensitizing effect of DLL4 on non-small cell lung cancer and its possible molecular mechanism.Methods: The expression level of DLL4 in NSCLC and its effect on prognosis were analyzed by bioinformatic technology,and the relationship between the expression level and a variety of clinicopathological parameters was verified by immune-histochemical method.NSCLC cell line A549 and SK-MES-1 cells were randomly divided into three groups: one group was transfected with lentivirus expression vector to up-regulate DLL4 expression,the other group was transfected with empty vector,and the third group was used as blank control.QRT-PCR and Western blot test were used to verify the transfection efficiency;CCK-8 test was used to detect the cell proliferation activity;transwell test was used to detect the cell migration ability of each group;after each group of cells were irradiated with gradient dose,plate cloning test was used to evaluate the effects of different levels of DLL4 expression on the radiosensitivity of the two cell lines;Western bolt test was used to detect the expression levels of VEGFA,PTEN and p-AKT proteins in A549 cells.Results: Compared with normal lung tissue,the low expression of DLL4 in NSCLC tissue was consistent with the results of bioinformatic data mining,and was related to tumordiameter,lymph node metastasis and distant metastasis.Compared with immortalized human normal lung epithelial cells BEAS-2B,the expression of DLL4 m RNA in NSCLC cell lineswas lower.Compared with the control group,over-expression of DLL4 could inhibit the proliferation and migration of non-small cell lung cancer cells,improve the radiosensitivity,decrease the expression of VEGFA,increase the expression of PTEN and decrease the expression level of p-AKT.Conclusions: DLL4 is low expressed in NSCLC.Overexpression of DLL4 can reduce the proliferation and migration ability of NSCLC cell line and increase radiosensitivity.The mechanism may be that DLL4 activates Notch signal pathway to inhibit the expression of VEGFA,promote the expression of PTEN and thus inhibit the phosphorylation of AKT.