Role and Mechanism of Complement C1q in Temozolomide Resistance in Glioblastoma
Objective:To investigate the role and mechanism of complement C1q in temozolomide(TMZ)resistance in glioblastoma multiforme(GBM).Methods:The expression patterns of complement C1q-related genes(C1QA,B and C)in GBM were mined by public database,and the expression levels of C1QA,B and C were detected by real-time fluorescence quantitative PCR(RT-qPCR).CCK8 method was used to determine the cell viability and half inhibitory concentration(IC50)of U251 and U251 drug-resistant strains(U251/TR),and flow cytometry was used to detect the apoptosis of U251 and U251/TR cells.Transwell assay was used to detect the migration ability of U251/TR cells.Western blot was used to detect the protein expression levels of complement C1 q A chain(C1QA)and O6-methylguanine-DNA methyltransferase(MGMT).Results:Bioinformatics analysis showed that C1QA,B and C were up-regulated in GBM,and C1QA and B were associated with tumor grade.RT-qPCR and Western blot confirmed that the expression of C1QA was decreased in U251/TR,and overexpression of C1QA in U251/TR could down-regulate IC50,increase TMZ-induced apoptosis and cell migration inhibition,and down-regulate MGMT protein levels.Conclusion:The level of C1QA in GBM decreased after TMZ resistance,and overexpression of C1QA can reverse the resistance of some GBM.
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