PDF(Pubmed)
Abstract：
As a chemotherapy agent, cisplatin (DDP) is often associated with drug resistance and gastrointestinal toxicity, factors that severely limit therapeutic efficacy in patients with ovarian cancer (OC). Naringin has been shown to increase sensitivity to cisplatin, but whether the intestinal microbiota is associated with this effect has not been reported so far. In this study, we applied a humanized mouse model for the first time to evaluate the reversal of cisplatin resistance by naringin, as well as naringin combined with the microbiota in ovarian cancer. The results showed that naringin combined with Bifidobacterium animalis subsp. lactis NCU-01 had an inhibitory effect on the tumor, significantly reducing tumor size (p<0.05), as well as the concentrations of serum tumor markers CA125 and HE4, increased the relative abundance of Bifidobacterium and Bacteroides, inhibit Toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB)-induced intestinal inflammation and increase the expression of intestinal permeability-associated proteins ZO-1 (p<0.001) and occludin (p<0.01). In conclusion, the above data demonstrate how naringin combined with Bifidobacterium animalis subsp. lactis NCU-01 reverses cisplatin resistance in ovarian cancer by modulating the intestinal microbiota, inhibiting the TLR4/NF-κB signaling pathway and modulating the p38MAPK signaling pathway.
摘要：
作为化疗药物,顺铂（DDP）通常与耐药性和胃肠道毒性有关，严重限制卵巢癌（OC）患者疗效的因素。柚皮苷已被证明可以增加对顺铂的敏感性，但是到目前为止，肠道微生物群是否与这种效应有关还没有报道。在这项研究中,我们首次应用人源化小鼠模型评价柚皮苷逆转顺铂耐药的作用,以及柚皮苷与卵巢癌微生物群的结合。结果表明，柚皮苷与动物双歧杆菌亚种联合使用。乳酸NCU-01对肿瘤有抑制作用，显著减小肿瘤大小（p<0.05），以及血清肿瘤标志物CA125和HE4的浓度，增加了双歧杆菌和拟杆菌的相对丰度，抑制Toll样受体4（TLR4）/核因子κB（NF-κB）诱导的肠道炎症，增加肠道通透性相关蛋白ZO-1（p<0.001）和occludin（p<0.01）的表达。总之,以上数据表明柚皮苷如何与动物双歧杆菌亚种结合。乳酸NCU-01通过调节肠道菌群逆转卵巢癌的顺铂耐药，抑制TLR4/NF-κB信号通路和调节p38MAPK信号通路。
