Research Paper Volume 16, Issue 2 pp 1336—1351
Cisplatin and doxorubicin chemotherapy alters gut microbiota in a murine osteosarcoma model
- 1 Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China
- 2 Department of Orthopedics, The Second Hospital of Shanxi Medical University, Shanxi Key Laboratory of Bone and Soft Tissue Injury Repair, Taiyuan, Shanxi 030001, P.R. China
- 3 Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan 030032, P.R. China
- 4 Department of Orthopedics, The Third People’s Hospital of Datong City, Datong, Shanxi 037006, P.R. China
- 5 Department of Orthopedics, JinZhong Hospital Affiliated to Shanxi Medical University, Jinzhong, Shanxi 030600, P.R. China
- 6 Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi 030013, P.R. China
Received: August 11, 2023 Accepted: December 1, 2023 Published: January 16, 2024
https://doi.org/10.18632/aging.205428How to Cite
Copyright: © 2024 Tian et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
The gut microbiota is closely associated with tumor progression and treatment in a variety of cancers. However, the alteration of the gut microbiota during the progression and chemotherapy of osteosarcoma remains poorly understood. This study aimed to explore the relationship between dysbiosis in the gut microbiota during osteosarcoma growth and chemotherapy treatment. We used BALB/c nude mice to establish osteosarcoma xenograft tumor models and administered cisplatin (CDDP) or doxorubicin (DOX) intraperitonially once every 2 days for a total of 5 times to establish effective chemotherapy models. Fecal samples were collected and processed for 16S rRNA sequencing to analyze the composition of the gut microbiota. We observed that the abundances of Colidextribacter, Lachnospiraceae_NK4A136_group, Lachnospiraceae_UCG-010, Lachnospiraceae_UCG-006, and Lachnoclostridium decreased, and the abundances of Alloprevotella and Enterorhabdus increased in the osteosarcoma mouse model group compared to those in the control group. In addition, genera, such as Lachnoclostridium and Faecalibacterium were more abundant in chemotherapy-treated mice than those in saline-treated mice. Additionally, we observed that alterations in some genera, including Lachnoclostridium and Colidextribacter in the osteosarcoma animal model group returned to normal after CDDP or DOX treatment. Furthermore, the function of the gut microbiota was inferred through PICRUSt2 (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), which indicated that metabolism-related microbiota was highly enriched and significantly different in each group. These results indicate correlations between dysbiosis of the gut microbiota and osteosarcoma growth and chemotherapy treatment with CDDP or DOX and may provide novel avenues for the development of potential adjuvant therapies.
Abbreviations
CDDP: cisplatin; DOX: doxorubicin; PICRUSt2: phylogenetic investigation of communities by reconstruction of unobserved states; OTUs: operational taxonomic units; PCoA: principal coordinate analysis; LEfSe: linear discriminant analysis coupled with effect size measurements; KEGG: Kyoto Encyclopedia of Genes and Genomes; COG: Clusters of Orthologous Groups of proteins; DMEM: Eagle’s medium; FBS: fetal bovine serum; BSA: bovine serum albumin.