PDF(Pubmed)
Abstract：
The microbiome is capable of modulating the bioavailability of chemotherapy drugs, mainly due to metabolizing these agents. Multiple cytostatic bacterial metabolites were recently identified that have cytostatic effects on cancer cells. In this study, we addressed the question of whether a set of cytostatic bacterial metabolites (cadaverine, indolepropionic acid and indoxylsulfate) can interfere with the cytostatic effects of the chemotherapy agents used in the management of breast cancer (doxorubicin, gemcitabine, irinotecan, methotrexate, rucaparib, 5-fluorouracil and paclitaxel). The chemotherapy drugs were applied in a wide concentration range to which a bacterial metabolite was added in a concentration within its serum reference range, and the effects on cell proliferation were assessed. There was no interference between gemcitabine, irinotecan, methotrexate or rucaparib and the bacterial metabolites. Nevertheless, cadaverine and indolepropionic acid modulated the Hill coefficient of the inhibitory curve of doxorubicin and 5-fluorouracil. Changes to the Hill coefficient implicate alterations to the kinetics of the binding of the chemotherapy agents to their targets. These effects have an unpredictable significance from the clinical or pharmacological perspective. Importantly, indolepropionic acid decreased the IC50 value of paclitaxel, which is a potentially advantageous combination.
摘要：
微生物组能够调节化疗药物的生物利用度，主要是由于代谢这些药物。最近鉴定出多种细胞抑制细菌代谢物对癌细胞具有细胞抑制作用。在这项研究中,我们解决了一组细胞抑制细菌代谢物(尸胺，吲哚丙酸和硫酸吲哚酯）可以干扰乳腺癌治疗中使用的化疗药物的细胞抑制作用（多柔比星，吉西他滨,伊立替康,甲氨蝶呤,rucaparib,5-氟尿嘧啶和紫杉醇)。化疗药物在较宽的浓度范围内应用，其中细菌代谢物以其血清参考范围内的浓度添加，并评估对细胞增殖的影响。吉西他滨之间没有干扰，伊立替康,甲氨蝶呤或鲁卡帕尼和细菌代谢产物。然而，尸胺和吲哚丙酸调节阿霉素和5-氟尿嘧啶抑制曲线的Hill系数。Hill系数的变化暗示化疗剂与其靶标的结合动力学的改变。从临床或药理学角度来看，这些作用具有不可预测的意义。重要的是,吲哚丙酸降低紫杉醇的IC50值，这是一个潜在的有利组合。
