Metformin Prevents Peritoneal Dissemination via Immune-suppressive Cells in the Tumor Microenvironment

Takanori Hirayama, Yasuhiro Nagata, Mikako Nishida, Mitsutoshi Matsuo, Shinichiro Kobayashi, Akira Yoneda, Kengo Kanetaka, Heiichiro Udono, Susumu Eguchi

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


Background/Aim: Metformin, a drug for type 2 diabetes, also exerts anticancer effects. This study addressed the immunological effects of metformin on peritoneal dissemination. Materials and Methods: We developed a mouse model of peritoneal dissemination via intraperitoneal injection of RLmale1, an X-ray-induced leukemia cell line, into BALB/c mice. Cell-surface markers, cytokine production, and myeloid-derived suppressor cells (MDSCs) were examined in cells from spleen and peritoneal lavage fluid. Results: Metformin-treated mice exhibited suppressed intraperitoneal tumor growth and extended survival, and these effects were lost in mice with severe combined immunodeficiency. MDSCs induction was inhibited in metformin-treated mice. Although MDSC mobilization into the peritoneal cavity was correlated with suppression of interferon-γ production by tumor-infiltrating lymphocytes, the T-helper 1 ability of these lymphocytes was preserved in metformin-treated mice. Conclusion: Our findings demonstrate the action of metformin on both intraperitoneal tumors and immune-suppressive cells and might contribute to the development of immunotherapy against peritoneal dissemination.

Original languageEnglish
Pages (from-to)4699-4709
Number of pages11
JournalAnticancer research
Issue number9
Publication statusPublished - 2019


  • Metformin
  • Myeloid derived suppressor cell
  • Peritoneal dissemination
  • Tumor microenvironment

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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