Li Hailong, Gao Xiufei, Chen Yian, Wang Mengqian, Xu Chuchu, Yu Qinghong, Jin Ying, Song Jiaqing, Zhu Qi
School of Green Intelligent Pharmaceutical Industry, Zhejiang Guangsha Vocational and Technical University of Construction, Dongyang, Zhejiang, China.
Department of Breast Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China.
Front Oncol. 2023 Jul 4;13:1121471. doi: 10.3389/fonc.2023.1121471. eCollection 2023.
Tamoxifen is an effective anti-tumor medicine, but evidence has been provided on tamoxifen-related inflammation as well as its impact on gut microbiota. In this study, we aimed to investigate tamoxifen-induced gut microbiota and inflammation alteration.
We established a BC xenograft mouse model using the MCF-7 cell line. 16S rRNA gene sequencing was used to investigate gut microbiota. qRT-PCR, western blotting, and cytometric bead array were used to investigate inflammation-related biomarkers. Various bioinformatic approaches were used to analyze the data.
Significant differences in gut microbial composition, characteristic taxa, and microbiome phenotype prediction were observed between control, model, and tamoxifen-treated mice. Furthermore, protein expression of IL-6 and TLR5 was up-regulated in tamoxifen-treated mice, while the mRNA of Tlr5 and Il-6, as well as protein expression of IL-6 and TLR5 in the model group, were down-regulated in the colon. The concentration of IFN-γ, IL-6, and IL12P70 in serum was up-regulated in tamoxifen-treated mice. Moreover, correlation-based clustering analysis demonstrated that inflammation-negatively correlated taxa, including and , were enriched in the model group, while inflammation-positively correlated taxa, including and , were enriched in the tamoxifen-treated group. Finally, colon histologic damage was observed in tamoxifen-treated mice.
Tamoxifen treatment significantly altered gut microbiota and increased inflammation in the breast cancer xenograft mice model. This may be related to tamoxifen-induced intestinal epithelial barrier damage and TLR5 up-regulation.
他莫昔芬是一种有效的抗肿瘤药物，但已有证据表明他莫昔芬会引发炎症以及对肠道微生物群产生影响。在本研究中，我们旨在探究他莫昔芬诱导的肠道微生物群和炎症变化。
我们使用MCF-7细胞系建立了乳腺癌异种移植小鼠模型。采用16S rRNA基因测序来研究肠道微生物群。运用qRT-PCR、蛋白质印迹法和细胞计数珠阵列来研究炎症相关生物标志物。使用各种生物信息学方法来分析数据。
在对照、模型和他莫昔芬治疗的小鼠之间，观察到肠道微生物组成、特征分类群和微生物组表型预测存在显著差异。此外，他莫昔芬治疗的小鼠中IL-6和TLR5的蛋白表达上调，而模型组中Tlr5和Il-6的mRNA以及结肠中IL-6和TLR5的蛋白表达下调。他莫昔芬治疗的小鼠血清中IFN-γ、IL-6和IL12P70的浓度上调。此外，基于相关性的聚类分析表明，模型组中炎症负相关的分类群（包括 和 ）富集，而他莫昔芬治疗组中炎症正相关的分类群（包括 和 ）富集。最后，在他莫昔芬治疗的小鼠中观察到结肠组织学损伤。
在乳腺癌异种移植小鼠模型中，他莫昔芬治疗显著改变了肠道微生物群并增加了炎症。这可能与他莫昔芬诱导的肠上皮屏障损伤和TLR5上调有关。
