Abstract：
Exosomes released from tumor cells treated with cancer-targeting drugs reflect altered metabolic processes within the cells. Therefore, metabolites in exosomes can be used as markers to predict the therapeutic response or identify therapeutic targets. In this study, metabolite changes in exosomes were investigated by co-administration of the herbal extract SH003 and docetaxel (DTX), which exert a synergistic anti-cancer effect on lung cancer cells. Exosomes released from cells treated with SH003 and DTX were purified, and untargeted metabolic profiling was performed by liquid chromatography-tandem mass spectrometry. Analysis of altered metabolic-based pathways showed that the combined treatment synergistically increased pyrimidine metabolism compared with single-drug treatment. Additionally, xenobiotic metabolism by cytochrome P450 was specifically increased in cells treated with the combination. However, the released exosomes and increased metabolites in exosomes did not affect the anti-cancer effect of SH003 and DTX. Therefore, our study suggests that metabolite profiling can be used to evaluate the efficacy of combined treatments. Furthermore, such exosome-based metabolism may facilitate understanding the physiological endpoints of combination therapy in human biofluids.
摘要：
用癌症靶向药物治疗的肿瘤细胞释放的外泌体反映了细胞内代谢过程的改变。因此,外泌体中的代谢物可用作标志物来预测治疗反应或确定治疗靶标。在这项研究中,通过共同施用草药提取物SH003和多西他赛（DTX）来研究外泌体的代谢物变化，对肺癌细胞发挥协同抗癌作用。纯化用SH003和DTX处理的细胞释放的外泌体，通过液相色谱-串联质谱法进行非靶向代谢分析。基于代谢途径改变的分析表明，与单药治疗相比，联合治疗协同增加了嘧啶代谢。此外,通过细胞色素P450的异源代谢在用该组合处理的细胞中特异性增加。然而,释放的外泌体和外泌体中增加的代谢物不影响SH003和DTX的抗癌作用.因此,我们的研究表明,代谢物谱分析可用于评估联合治疗的疗效.此外，这种基于外泌体的代谢可能有助于理解人类生物流体联合治疗的生理终点。
