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Bifidobacterium-derived membrane vesicles inhibit triple-negative breast cancer growth by inducing tumor cell apoptosis

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Abstract

Background

Bacterial outer membrane vesicles have gained increasing attention for its antitumor effect and application in drug delivery. However, the bacterial membrane vesicles (MVs) that are secreted by Gram-positive bacteria are rarely mentioned. Bifidobacterium has a certain anti-tumor effect, but there is a certain risk when injected into human body. Here we investigated the potential of Bifidobacterium-derived membrane vesicles (B-MVs) as therapeutic agents to treat triple-negative breast cancer.

Methods and results

Firstly, we discovered that Bifidobacterium can produce B-MVs and isolated them. In vivo, we found that B-MVs can inhibit tumor growth in mice and the mice were in good state. H&E staining displayed extensive apoptotic cells in tumor tissues. Western blotting and immunohistochemistry showed that B-MVs increased the expression of Bax, while decreased the expression of Bcl-2. These results suggested that B-MVs may induce apoptosis of tumor cells in vivo. Furthermore, to further confirm this phenomenon, we conducted experiments in vitro. Hoechst 33,258 staining assay, flow cytometry and western blotting also demonstrated B-MVs promoted cell apoptosis in vitro.

Conclusions

We speculate B-MVs may inhibit tumor growth by inducing tumor cell apoptosis in triple-negative breast cancer, which provided a new direction in the treatment of TNBC.

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Data availability

The data presented in this study are available on request from the corresponding author.

Abbreviations

MVs:

Membrane vesicles

OMVs:

Outer membrane vesicles

B-MVs:

Bifidobacterium-derived membrane vesicles

TNBC:

Triple-negative breast cancer

ER:

Estrogen receptor

PR:

Progesterone receptor

HER-2:

Human epidermal growth factor receptor 2

V. cholera :

Vibrio cholera

TEM:

Transmission electron microscope

NTA:

Nanoparticle tracking analysis

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Acknowledgements

The authors would like to thank the Chongqing Medical University, State Key Laboratory of Ultrasound in Medicine and Engineering for providing the necessary facilities to conduct this study.

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Authors

Contributions

Conceptualization: YJ. Methodology: YJ, LW, BY, GM, ZC, JM and XC. Software: YJ. Writing—original draft preparation: YJ. Writing—review and editing: YJ. Supervision: LF and ZW.

Corresponding authors

Correspondence to Liaoqiong Fang or Zhibiao Wang.

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Conflict of interest

The authors declare no conflict of interest.

Ethics approval

All the experimental procedures were approved by the animal ethics committee of Chongqing Medical University (Date 2022.6.28/No2022155). All procedures involving animals were conducted with the guidelines of the Institutional Animal Care and Use Committee of Chongqing Medical University.

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Jiang, Y., Wang, L., Yang, B. et al. Bifidobacterium-derived membrane vesicles inhibit triple-negative breast cancer growth by inducing tumor cell apoptosis. Mol Biol Rep 50, 7547–7556 (2023). https://doi.org/10.1007/s11033-023-08702-z

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