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The exosome secretion inhibitor neticonazole suppresses intestinal dysbacteriosis-induced tumorigenesis of colorectal cancer

  • Lei Gu
  • Yidong Xu
  • Wangyan Xu
  • Meng Li
  • Hui Su
  • Cong Li
  • Zhongchen LiuEmail author
PHASE I STUDIES

Summary

Colorectal cancer (CRC) is the most frequently encountered malignancy associated with the rectum or colon, and accumulating evidences have implicated intestinal dysbacteriosis (IDB, disruption of gut microbiome) and exosomes in the pathology of CRC. We aimed to investigate the effect of IDB on exosome secretion in a CRC xenograft mouse model. An IDB mouse model was established and was inoculated with the CRC cell line SW480 as a xenograft tumor. Tumor growth was monitored for 15 days in sham and IDB mice, after which blood was collected to assess serum exosome secretion. A novel exosome secretion inhibitor, neticonazole, was administered to IDB mice bearing CRC xenograft tumors, followed by monitoring of tumor growth and mouse survival. Western blot analysis was performed in xenograft tumors to investigate the underlying molecular mechanism. IDB promoted CRC xenograft tumor growth and exosome secretion, which could be inhibited by the exosome secretion inhibitor neticonazole. Moreover, neticonazole treatment significantly improved the survival of IDB mice with CRC xenograft tumors, likely through increasing apoptosis of CRC xenograft tumor cells. The exosome secretion inhibitor neticonazole may serve as a promising therapeutic candidate against CRC by suppressing IDB-induced CRC tumorigenesis.

Keywords

Intestinal dysbacteriosis Colorectal cancer Exosome Neticonazole 

Abbreviations

CRC

Colorectal cancer

IDB

Intestinal dysbacteriosis

Notes

Funding

This study was supported by the National Natural Science Foundation of China (81272720).

Compliance with ethical standards

Conflicts of interest

The authors declare that there are no conflicts of interest.

Research involving human participants and/or animals

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Informed consent

Not applicable.

Supplementary material

10637_2019_759_MOESM1_ESM.pdf (120 kb)
ESM 1 (PDF 120 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Lei Gu
    • 1
  • Yidong Xu
    • 1
  • Wangyan Xu
    • 2
  • Meng Li
    • 3
  • Hui Su
    • 2
  • Cong Li
    • 1
  • Zhongchen Liu
    • 1
    Email author
  1. 1.Department of General Surgery, Shanghai Tenth People’s Hospital, School of MedicineTongji UniversityShanghaiChina
  2. 2.Anhui University of Science and TechnologyHuainanChina
  3. 3.School of Medicine Tongji UniversityShanghaiChina

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