Inhibitory effects of methyltransferase inhibitor SGI-1027 on migration and invasion of lung adenocarcinoma cells and its regulatory effect on methylation level of SPG20 gene
Objective To analyze the inhibitory effects of methyltransferase inhibitor SGI-1027 on the migration and invasion of lung adenocarcinoma A549 cells and its regulatory effect on the methylation level of spastic paraplegia-20(SPG-20)gene,in order to explore the effect and mechanism of methyltransferase inhibitor on the migration and invasion of lung adenocarcinoma cells.Methods Different concentrations of methyltransferase inhibitor SGI-1027 were used to treat lung adenocarcinoma A549 cells,and the cell proliferation activity was measured by MTT method.The optimal concentration of SGI-1027 was determined as 7.5 µmol/L,which was used as the concentration for subsequent experiments.A549 cells were divided into the SGI-1027 group and dimethyl sulfoxide(DMSO)group.Cells in the SGI-1027 group were added with SGI-1027 in the medium,and cells in the DMSO group were added with DMSO.After culturing the cells for 48 h,the cell migration ability was observed by scratch healing test,and the cell invasion ability was observed by Transwell chamber test.DNA methyltransferase 3b(DNMT3b)and SPG20 mRNA were detected by qRT-PCR,SPG20 gene methylation lev-els were detected by pyrosequencing,and DNMT3b and SPG20 proteins were detected by Western blotting.Results At 48 h of culture,compared with the DMSO group,SGI-1027 group had smaller migration distance and fewer transmem-brane cells(both P<0.05).Compared with the DMSO group,the relative expression levels of DNMT3b mRNA and pro-tein decreased,while the relative expression levels of SPG20 mRNA and protein increased in the SGI-1027 group(all P<0.05).The methylation rate of SPG20 gene in the SGI-1027 group was lower than that in the DMSO group(P<0.05).Conclusions Methyltransferase inhibitor SGI-1027 can inhibit the migration and invasion of lung adenocarcinoma A549 cells,and reduce the methylation level of SPG20.SGI-1027 may inhibit the migration and invasion of lung adenocarcino-ma cells by down-regulating the intracellular SPG20 methylation level.
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