The purpose of this study was to investigate the inhibitory effect of ZH-1 ((6S,9aS,6aR,9bR)-6-(phenylcarbonyl)-6,6a,9a,9b-tetrahydro-8H-azolidino[3,4-a]b enzo [e]indolizine-7,9-dione) and its potential interactions with gemcitabine in A549 cells. MTT assay showed that the combined use of gemcitabine and ZH-1 presented a significant inhibition effect on A549 cell growth with the cell viability from 82.3 ± 5.6% to 51.0 ± 6.6%. The CI value was 0.60 suggesting a synergistic effect between these two drugs. HPLC-MS/MS data indicated that combined treatment with gemcitabine and ZH-1 induced a significant decrease in deoxyadenosine triphosphate, deoxycytidine triphosphate, deoxyguanosine triphosphate and deoxythymidine triphosphate levels compared with use of gemcitabine alone. Five RNs including as well as seven dRNs were considered to be significantly contributive to the discrimination of samples. Furthermore, western blotting analysis revealed that the combination treatment caused A549 cell apoptosis via the intrinsic pathway by up-regulating Bax/Bcl-2 ratio, activating caspase-9, caspase-3 and poly-ADP-ribose polymerase, and promoting caspase-7, caspase-9 and poly-ADP-ribose polymerase cleavage. Collectively, the combined treatment with gemcitabine and ZH-1 exerted a strong synergistic action on anticancer activity through growth inhibition, perturbations in ribonucleotides and deoxyribonucleotides and the activation of intrinsic apoptotic signaling pathway.

这项研究的目的是研究ZH-1（（6S，9aS，6aR，9bR）-6-（苯基羰基）-6,6a，9a，9b-四氢-8H-偶氮立尼丁的抑制作用[3,4- a] b enzo [e] indolizine-7,9-dione）及其与吉西他滨在A549细胞中的潜在相互作用。MTT分析表明，吉西他滨和ZH-1的联合使用对A549细胞的生长具有显着的抑制作用，细胞活力从82.3±5.6％增至51.0±6.6％。CI值为0.60，表明这两种药物之间具有协同作用。HPLC-MS / MS数据表明，与单独使用吉西他滨相比，吉西他滨和ZH-1的联合治疗引起三磷酸脱氧腺苷，三磷酸脱氧胞苷，三磷酸脱氧鸟苷和脱氧胸苷的水平显着降低。五个RN（包括七个dRN）被认为是对样品鉴别的重要贡献。此外，western blotting分析显示，联合处理通过上调Bax / Bcl-2比，激活caspase-9，caspase-3和poly-ADP-核糖聚合酶并促进caspase-7经由内在途径引起A549细胞凋亡。 ，caspase-9和聚ADP-核糖聚合酶裂解。总的来说，吉西他滨和ZH-1的联合治疗通过抑制生长，干扰核糖核苷酸和脱氧核糖核苷酸以及激活内在的凋亡信号通路，对抗癌活性产生强大的协同作用。免疫印迹分析表明，联合治疗通过上调Bax / Bcl-2比，激活caspase-9，caspase-3和poly-ADP-核糖聚合酶并促进caspase-7，caspase经由内在途径引起A549细胞凋亡。 -9和聚-ADP-核糖聚合酶裂解。总的来说，吉西他滨和ZH-1的联合治疗通过抑制生长，干扰核糖核苷酸和脱氧核糖核苷酸以及激活内在的凋亡信号通路，对抗癌活性产生强大的协同作用。免疫印迹分析表明，联合治疗通过上调Bax / Bcl-2比，激活caspase-9，caspase-3和poly-ADP-核糖聚合酶并促进caspase-7，caspase经由内在途径引起A549细胞凋亡。 -9和聚-ADP-核糖聚合酶裂解。总的来说，吉西他滨和ZH-1的联合治疗通过抑制生长，干扰核糖核苷酸和脱氧核糖核苷酸以及激活内在的凋亡信号通路，对抗癌活性产生强大的协同作用。