Expression Of PTP1B In Gliomas And Its Therapeutic Significance For Glioma

Objective: To investigate whether knockdown of PTP1 B inhibits proliferation,migration and invasion of glioma cells,as well as potential mechanisms.Methods: The glioma cell line U87 was cultured in vitro.The PTP1 B interference plasmid was designed and synthesized,transfected into U87 cells with lentivirus as vector,and transfected into U87 cells with empty plasmid as control group,which was recorded as empty group.The protein expression level of PTP1 B in U87 cells of the empty group and the PTP1 B gene-specific shPTP1 B group was determined by Western blotting,to verify the efficiency of gene knockdown of PTP1 B expression.After confirming the decrease of PTP1 B expression level in shPTP1 B group.The effect of PTP1 B on the proliferation of U87 cells was examined by MTT proliferation assay and colony formation assay.Cell cycle changes of U87 cells after PTP1 B knockdown were detected by flow cytometry.The expression levels of cyclin CDK,E2 F,CyclinD1 and P21 protein were detected by western blot.A cell scratch test was performed to examine the migration ability of U87 cells in the shNC group and the shPTP1 B group.Transwell chamber assay was used to detect the invasive ability of U87 cells in shNC group and shPTP1 B group.Finally,the expression levels of Src/Ras,PI3K/AKT,p62DOK/RasGAP-related signals(Src,pSrc418,AKT,P-AKT,ERK,p-ERK)were detected by Western blot,revealing that the molecular mechanism of PTP1 B affects the growth of gliomas.Results: The PTP1 B interference plasmid was prepared and transfected into the glioma cell line U87 with lentivirus as a vector.The results showed that western blot showed that the expression level of PTP1 B protein in U87 cells transfected with shPTP1 B was significantly decreased.MTT and colony formation experiments showed that the proliferation of U87 cells was significantly inhibited after PTP1 B knockdown;cell scratch assay and Transwell chamber assay showed that PTP1 B knockdown significantly inhibited the migration and invasion of U87 cells.Flow cytometry showed that PTP1 B knockdown resulted in cycle inhibition of U87 cells.Western blot revealed that PTP1 B knockdown could decrease the expression level of cell cycle associated protein,and in Src-mediated signaling pathways,the expression levels of p-Src418,p-AKT,and p-Erk were down-regulated.Conclrsions: Through this study,our data indicate that PTP1 B plays a key role in theproliferation,metastasis and invasion of glioma cells.Down-regulation of PTP1 B gene significantly inhibits tumor growth in vitro,and migration and infiltration of tumor cells in vitro are also inhibited.This is related to the aberrant expression of Src,which increases the activity of intracellular Src and is involved in the regulation of malignant phenotypes such as proliferation,migration,invasion and drug resistance of glioma cells.Therefore,PTP1 B may be a new biomarker reflecting the invasiveness of gliomas.Targeted inhibition of PTP1 B may be a new approach to the treatment of glioma.However,whether PTP1 B can be used as a therapeutic target for glioma remains to be further studied.