Influence of gemcitabine chemotherapy on the microbiota of pancreatic cancer xenografted mice

Concetta Panebianco, Kaarel Adamberg, Madis Jaagura, Massimiliano Copetti, Andrea Fontana, Signe Adamberg, Kaia Kolk, Raivo Vilu, Angelo Andriulli, Valerio Pazienza

Research output: Contribution to journalArticlepeer-review

Abstract

Background and aims: Pancreatic ductal adenocarcinoma (PDAC) represents the fourth cause of cancer-related death. We aimed to evaluate whether gemcitabine treatment shapes the gut microbiota in a model of PDAC xenografted mice. Materials and methods: Pancreatic cancer xenograft mice were subjected to gemcitabine injection once per week for 3 weeks to assess the tumor volume as compared to control mice injected with normal saline solution. The composition of fecal microbiota, the activation of NF-kB pathway in cancer tissues and the serum metabolomics were further analyzed. Results: Gemcitabine considerably decreases the proportion of Gram- positive Firmicutes (from about 39 to 17%) and the Gram- negative Bacteroidetes (from 38 to 17%) which are the two dominant phyla in the gut of tumor-bearing control mice. This downshift was replaced by an increase of Proteobacteria (Escherichia coli and Aeromonas hydrophila) from 15 up to 32% and Verrucomicrobia (Akkermansia muciniphila) from 5 to 33% in the gut of drug-receiving mice. An overall increase in inflammation-associated bacteria was observed upon gemcitabine. Consistently, activation of the NF-kB canonical pathway was found in cancer tissues from gemcitabine-treated mice. Serum metabolomics revealed a significant decrease of the purine compounds inosine and xanthine, and a decreasing trend for their metabolically-related molecule hypoxanthine. Discussion: Understanding chemotherapy side effects may explain the lack of activity or the chemoresistant processes and it may help to set up strategies to improve the effectiveness of therapy.

Original languageEnglish
Pages (from-to)773-782
Number of pages10
JournalCancer Chemotherapy and Pharmacology
Volume81
Issue number4
DOIs
Publication statusPublished - Apr 1 2018

Keywords

  • Gemcitabine
  • Inflammation
  • Microbiota
  • Pancreatic cancer

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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