OBJECTIVE The aim of the present study was to investigate the anti-tumor effect and mechanism of a novel compound,C_3C_(12)PPD,a bioactive unnatural ginsenoside by metabolically engi.neered yeasts based on a new UDP-g...OBJECTIVE The aim of the present study was to investigate the anti-tumor effect and mechanism of a novel compound,C_3C_(12)PPD,a bioactive unnatural ginsenoside by metabolically engi.neered yeasts based on a new UDP-glycosyl-transferase from Bacillus subtilis.METHODS MTT assay was used to analyze the anti-proliferation activity of C_3C_(12)PPD in vitro.The effect of anti-tumor activity was observed by mouse Lewis xenograft model in vivo.The effects of C_3C_(12)PPD on suppressing the angio.genesis and invasion of A549 cells were investigated in vitro using Transwell and tube formation assays.RNAseq was used to find tagets of C_3C_(12)PPD.Western blotting was performed to investigate the expres.sion level of proteins in tumor tissues treated with C_3C_(12)PPD.RESULTS C_3C_(12)PPD could inhibit the growth of lung cancer in vitro and in vivo.At the dosage of 10.0 mg · kg^(-1),C_3C_(12)PPD inhibited tumor growth by 40.0%(P<0.05) in tumor weight in mouse Lewis xenograft.The inhibition of tube formation was 77.5%(P<0.01) and 80.3%(P<0.01) following treatment with 1×10^(-4) and 2×10^(-4) mol·L^(-1) C_3C_(12)PPD for 5 h,whereas the proliferation of EA.hy926 cells was not influenced under the above concentrations.Under the concentrations of 1×10^(-4) mol·L^(-1),C_3C_(12)PPD inhibited invasive ability of A549 cells(P<0.05).The results of RNAseq susgested that antitumor activity of C_3C_(12)PPD were associated with epithelial-mesenchymal transition(EMT) and angiogenesis.Moreover,the proteins related to EMT,Raf/MEK/ERK and AKT/mTOR signal pathways were effected by C_3C_(12)PPD analysed by western blotting.CONCLUSION These data suggested that C_3C_(12)PPD was able to supress lung cancer through inhibit EMT,invision and angiogenesis.展开更多
文摘OBJECTIVE The aim of the present study was to investigate the anti-tumor effect and mechanism of a novel compound,C_3C_(12)PPD,a bioactive unnatural ginsenoside by metabolically engi.neered yeasts based on a new UDP-glycosyl-transferase from Bacillus subtilis.METHODS MTT assay was used to analyze the anti-proliferation activity of C_3C_(12)PPD in vitro.The effect of anti-tumor activity was observed by mouse Lewis xenograft model in vivo.The effects of C_3C_(12)PPD on suppressing the angio.genesis and invasion of A549 cells were investigated in vitro using Transwell and tube formation assays.RNAseq was used to find tagets of C_3C_(12)PPD.Western blotting was performed to investigate the expres.sion level of proteins in tumor tissues treated with C_3C_(12)PPD.RESULTS C_3C_(12)PPD could inhibit the growth of lung cancer in vitro and in vivo.At the dosage of 10.0 mg · kg^(-1),C_3C_(12)PPD inhibited tumor growth by 40.0%(P<0.05) in tumor weight in mouse Lewis xenograft.The inhibition of tube formation was 77.5%(P<0.01) and 80.3%(P<0.01) following treatment with 1×10^(-4) and 2×10^(-4) mol·L^(-1) C_3C_(12)PPD for 5 h,whereas the proliferation of EA.hy926 cells was not influenced under the above concentrations.Under the concentrations of 1×10^(-4) mol·L^(-1),C_3C_(12)PPD inhibited invasive ability of A549 cells(P<0.05).The results of RNAseq susgested that antitumor activity of C_3C_(12)PPD were associated with epithelial-mesenchymal transition(EMT) and angiogenesis.Moreover,the proteins related to EMT,Raf/MEK/ERK and AKT/mTOR signal pathways were effected by C_3C_(12)PPD analysed by western blotting.CONCLUSION These data suggested that C_3C_(12)PPD was able to supress lung cancer through inhibit EMT,invision and angiogenesis.
