Effect Of DNA Methylation Transferase-1 Inhibitor DC₅17 On Proliferation,Invasion And Autophagy Of Glioma Cells

Background Glioma is the most common malignant tumor of the brain.Due to the unlimited growth of glioma cells and poor prognosis,patients with glioma often need radiotherap y and chemotherap y after operation.DC₅17 is a new type of specific non-nucleoside DNMT1 inhibitor,which has a significant inhibitory effect on DNMT1.In this stud y,we investigated the role of DC₅17 in U251 and LN18 glioma cells.The results showed that DC₅17 could significantl y inhibit the proliferation of glioma cells in a dose-and time-dependent manner.In addition,DC₅17 can also induce autophagy of glioma cells.To sum up,this stud y has a good understanding of the role of DC₅17 in glioma cells,and provides new ideas and methods for clinical chemotherap y of glioma.Objective To study the effects of a new specific non-nucleoside DNA meth yltransferase-1（DNMT1）inhibitor DC₅17 on the proliferation,invasion and autophagy o f human glioma cell lines U251 and LN18 cells.Methods U251 and LN18 glioma cell lines were treated with different concentrations of DC₅17 for indicated time.CCK-8 assay was used to detect the proliferation of glioma cells.Transwell invasion assay was used for detecting glioma cells invasion.Key autophagy-related protein expression in glioma cells was detected b y immunofluorescence.QRT-PCR assay was used to detect the expression of DNMT1 mRNA.Western blotting assay was performed to detect DNMT1 and autophagy,proliferation and invasion-related proteins levels in glioma cells.Results Compared with control group,DC₅17 inhibited the proliferation and invasion of glioma cells as well as expression of proliferation-associated protein PCNA and invasi on-ralated protein MMP-9 in a time and dose-dependent manner.Furthermore,DC₅17 induced glioma cells autophagy and up-regulated levels of key autophagy protein LC3 B.The autophagy inhibitor Lys05 could partiall y reversed the inhibitory effect of DC₅17 on glioma cell s proliferation.In addition,low concentration of DC₅17 did not significant effect on proliferation of normal astrocytes.Conclusion DC₅17 inhibited glioma cells proliferation,invasion,and induced glioma cells autophagy via regulating proliferation,invasion and autophagy-related proteins.