Impact of dexmedetomidine on malignant biological behavior of gastric cancer cells through immune regulation mechanism mediated by cGAS-STING pathway
Objective:To investigate the effects of dexmedetomidine(DEX)on the malignant biological behavior of gastric cancer(GC)cells through the immune regulation mechanism mediated by cyclic GMP-AMP synthase-stimulator of interferon gene(cGAS-STING)pathway.Methods:GC cell line MGC-803 was randomly divided into Control group(blank medium treatment),DEX low concentration group(DEX-L group,1 ng/ml),DEX medium concentration group(DEX-M group,10 ng/ml),DEX high concentra-tion group(DEX-H group,100 ng/ml)and DEX high concentration+cGAS inhibitor RU.521 group(DEX-H+RU.521 group,100 ng/ml DEX+1.0 µmol/L RU.521).Cell proliferation was detected by CCK-8 method.Cell scratch test was used to detect the migration ability of cells in each group.Transwell test was used to detect the invasive ability of cells in each group.The apoptosis rate was detected by flow cytometry.The levels of IL-2,interferon gamma(IFN-γ)and tumor necrosis factor alpha(TNF-α)in cells were detected by ELISA.Real time-fluorescent quantitative PCR(RT-qPCR)was applied to detect the expression levels of cGAS,STING and interferon typeⅠ(IFN-Ⅰ)mRNA.Western blot was used to detect the expressions of cGAS,STING,Bax,CyclinD1,matrix metalloproteinase 9(MMP9),N-cadherin,Vimentin,E-cadherin,Caspase3,Caspase8 and their shear type and phosphorylation level of TANK-binding kinase 1(TBK1)and interferon regulatory factor 3(IRF3).Results:Compared with Control group,the cell migration rate,number of cell invasions,TNF-α level,CyclinD1,MMP9,N-cadherin,Vimentin protein expressions in MGC-803 cells in DEX-M and DEX-H groups were decreased obviously(P<0.05),the growth inhibition rate(48 h,72 h),apoptosis rate,IL-2,IFN-γ,Bax,E-cadherin,Cleaved Caspase3,Cleaved Caspase8 protein expression levels,cGAS,STING,IFN-Ⅰ mRNA levels and protein expression levels and phosphorylation levels of TBK1 and IRF3 were increased obviously(P<0.05).RU.521 weakened the inhibitory effects of DEX on the proliferation,migration and invasion of GC cells and the ability to induce apoptosis,and alleviated the improvement on immune function.Conclusion:DEX may inhibit the proliferation,migration and invasion of GC cells and induce apoptosis of GC cells by acti-vating cGAS-STING pathway mediated immune regulation.
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