Dichloroacetate And Vitamin C Synergistically Suppress Proliferation,migration And Invasion In Glioma Cell U87 And U251

Objective:To investigate the effects of Dichloroacetate（DCA）combine with Vitamin C（VC）on the malignant behavior of glioma U87 and U251 cells,as well as exploring the potential mechanism..Methods:U87 and U251 cells were treated with different concentrations of DCA alone or in combination with 5 mmol·L^-1VC.The proliferation rate of each group was detected by CCK-8 method and the cooperative index was calculated.U87 and U251cells were treated with DMSO,15 mmol·L^-1DCA,5 mmol·L^-1VC and their combination.The changes of clonal formation,reactive oxygen species content,apoptosis,cell cycle,migration and invasion were detected via in vitro experiments,while the proliferation of U251 cells in vivo in each group was detected by subcutaneous tumor-forming model.Western blotting was used to detect the expression levels and degradation rates of BCL2A1 and CDC25A in each group of cells after network pharmacological analysis of DCA and VC targets and their value in glioma,as well as determining the expression levels of CDK4,CDK6,Cytochrome C,Caspase7 and Cleave-Caspase7.Results:The combined index of 15 mmol·L^-1DCA and 5 mmol·L^-1VC was the highest.Compared with the control and single drug groups,the clonal formation,migration and invasion ability of cells in combination group in vitro were significantly decreased,the proliferation rate in vivo was also decreased,and the content of reactive oxygen species,apoptosis rate and G1 phase arrest rate were significantly increased.BCL2A1 and CDC25A proteins are important targets of DCA and VC in glioma.Compared with the control and single-drug groups,the expression levels of BCL2A1,CDC25A,CDK4,and CDK6 in the combination group were significantly decreased,and the expression levels of Cytochrome C and Cleaved caspase7 were significantly increased,and the protein degradation rates of BCL2A1 and CDC25A were significantly increased in the combination group.Conclusions:VC can cooperate with DCA to promote the degradation of BCL2A1 and CDC25A,and inhibit the malignant behavior of glioma cells...