Abstract
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 language | English |
|---|---|
| Pages (from-to) | 4699-4709 |
| Number of pages | 11 |
| Journal | Anticancer research |
| Volume | 39 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - Jan 1 2019 |
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Keywords
- Metformin
- Myeloid derived suppressor cell
- Peritoneal dissemination
- Tumor microenvironment
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Metformin Prevents Peritoneal Dissemination via Immune-suppressive Cells in the Tumor Microenvironment. / Hirayama, Takanori; Nagata, Yasuhiro; Nishida, Mikako; Matsuo, Mitsutoshi; Kobayashi, Shinichiro; Yoneda, Akira; Kanetaka, Kengo; Udono, Heiichiro; Eguchi, Susumu.
In: Anticancer research, Vol. 39, No. 9, 01.01.2019, p. 4699-4709.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Metformin Prevents Peritoneal Dissemination via Immune-suppressive Cells in the Tumor Microenvironment
AU - Hirayama, Takanori
AU - Nagata, Yasuhiro
AU - Nishida, Mikako
AU - Matsuo, Mitsutoshi
AU - Kobayashi, Shinichiro
AU - Yoneda, Akira
AU - Kanetaka, Kengo
AU - Udono, Heiichiro
AU - Eguchi, Susumu
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
KW - Metformin
KW - Myeloid derived suppressor cell
KW - Peritoneal dissemination
KW - Tumor microenvironment
UR - http://www.scopus.com/inward/record.url?scp=85072190737&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85072190737&partnerID=8YFLogxK
U2 - 10.21873/anticanres.13652
DO - 10.21873/anticanres.13652
M3 - Article
VL - 39
SP - 4699
EP - 4709
JO - Anticancer Research
JF - Anticancer Research
SN - 0250-7005
IS - 9
ER -