Metformin combined with local irradiation provokes abscopal effects in a murine rectal cancer model

Although preoperative chemoradiation therapy can down-stage locally advanced rectal cancer (LARC), it has little effect on distant metastases. Metformin exerts an anti-cancer effect partly through the activation of host immunity. LuM1, a highly lung metastatic subclone of colon 26, was injected subc...

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Bibliographic Details
Published in:Scientific reports Vol. 12; no. 1; pp. 7290 - 12
Main Authors: Tojo, Mineyuki, Miyato, Hideyo, Koinuma, Koji, Horie, Hisanaga, Tsukui, Hidenori, Kimura, Yuki, Kaneko, Yuki, Ohzawa, Hideyuki, Yamaguchi, Hironori, Yoshimura, Kotaro, Lefor, Alan Kawarai, Sata, Naohiro, Kitayama, Joji
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 04.05.2022
Nature Publishing Group
Nature Portfolio
Subjects:
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631/67
692/4020
692/4028
Animals
Antidiabetics
Cancer
Cancer therapies
CD4 antigen
CD8 antigen
CD8-Positive T-Lymphocytes
Cell activation
Cell-mediated immunity
Chemoradiotherapy
Colorectal cancer
Combined treatment
Flow cytometry
Humanities and Social Sciences
Immunohistochemistry
Irradiation
Lung cancer
Lung Neoplasms - pathology
Lungs
Lymphocytes T
Metastases
Metastasis
Metformin
Metformin - pharmacology
Mice
Mice, Inbred BALB C
multidisciplinary
Phenotypes
Radiation
Rectal Neoplasms - drug therapy
Rectal Neoplasms - radiotherapy
Rectum
Science
Science (multidisciplinary)
Spleen
Tumors
γ-Interferon
ISSN:2045-2322, 2045-2322
Online Access:Get full text
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Summary:Although preoperative chemoradiation therapy can down-stage locally advanced rectal cancer (LARC), it has little effect on distant metastases. Metformin exerts an anti-cancer effect partly through the activation of host immunity. LuM1, a highly lung metastatic subclone of colon 26, was injected subcutaneously (sc) in BALB/c mice and treated with metformin and/or local radiation (RT). Lung metastases and the primary tumors were evaluated and the phenotypes of immune cells in the spleen and lung metastases were examined with flow cytometry and immunohistochemistry. Local RT, but not metformin, partially delayed the growth of sc tumor which was augmented with metformin. Lung metastases were unchanged in metformin or RT alone, but significantly reduced in the combined therapy. The ratios of splenic T cells tended to be low in the RT group, which were increased by the addition of metformin. IFN-γ production of the splenic CD4(+) and CD8(+) T cells was enhanced and CD49b (+) CD335(+) activated NK cells was increased after combined treatment group. Density of NK cells infiltrating in lung metastases was increased after combination treatment. Metformin effectively enhances local and abscopal effects of RT though the activation of cell-mediated immunity and might be clinically useful for LARC.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-022-11236-2