Potential risk of tamoxifen: gut microbiota and inflammation in mice with breast cancer

Frontiers in Oncology

Oncology

Xiufei Gao¹  Qi Zhu¹  Chuchu Xu²  Jiaqing Song²  Yian Chen²  Mengqian Wang²  Qinghong Yu²  Ying Jin²  Hailong Li³ 

[1] Department of Breast Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China;First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China;School of Green Intelligent Pharmaceutical Industry, Zhejiang Guangsha Vocational and Technical University of Construction, Dongyang, Zhejiang, China;

关键词: breast cancer;    gut microbiota;    TLR5;    inflammation;    tamoxifen;   

DOI  :  10.3389/fonc.2023.1121471

 received in 2022-12-11, accepted in 2023-05-31,  发布年份 2023

来源: Frontiers

【 摘 要 】

ObjectiveTamoxifen 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.MethodsWe 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.ResultsSignificant 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 Lachnospiraceae-UCG-006 and Anaerotruncus, were enriched in the model group, while inflammation-positively correlated taxa, including Prevotellaceae_UCG_001 and Akkermansia, were enriched in the tamoxifen-treated group. Finally, colon histologic damage was observed in tamoxifen-treated mice.ConclusionTamoxifen 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.

【 授权许可】

Unknown   
Copyright © 2023 Li, Gao, Chen, Wang, Xu, Yu, Jin, Song and Zhu