Metformin combined with local irradiation provokes abscopal effects in a murine rectal cancer model.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
04 05 2022
04 05 2022
Historique:
received:
17
12
2021
accepted:
18
04
2022
entrez:
4
5
2022
pubmed:
5
5
2022
medline:
7
5
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35508498
doi: 10.1038/s41598-022-11236-2
pii: 10.1038/s41598-022-11236-2
pmc: PMC9068771
doi:
Substances chimiques
Metformin
9100L32L2N
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7290Informations de copyright
© 2022. The Author(s).
Références
Cancer Prev Res (Phila). 2010 Nov;3(11):1451-61
pubmed: 20947488
Clin Cancer Res. 2018 Apr 15;24(8):1891-1904
pubmed: 29363526
J Cancer Res Clin Oncol. 2016 Jun;142(6):1377-85
pubmed: 27011019
Oncoimmunology. 2014 Apr 25;3:e28518
pubmed: 25071979
PLoS One. 2015 Nov 23;10(11):e0143596
pubmed: 26599019
Clin Cancer Res. 2005 May 1;11(9):3353-62
pubmed: 15867235
Cancer Treat Rev. 2017 Apr;55:150-162
pubmed: 28399491
Cancer Immunol Res. 2017 Jan;5(1):3-8
pubmed: 28052991
Anticancer Res. 2019 Sep;39(9):4699-4709
pubmed: 31519569
Lancet Oncol. 2021 Jan;22(1):29-42
pubmed: 33301740
Mol Cell. 2018 Aug 16;71(4):606-620.e7
pubmed: 30118680
JAMA Oncol. 2021 Sep 01;7(9):1333-1341
pubmed: 34323924
J Clin Oncol. 2008 Aug 1;26(22):3687-94
pubmed: 18669453
Lancet Oncol. 2009 Jul;10(7):718-26
pubmed: 19573801
N Engl J Med. 2017 Nov 16;377(20):1919-1929
pubmed: 28885881
Semin Cancer Biol. 2012 Aug;22(4):275-81
pubmed: 22313874
J Diabetes Res. 2017;2017:5063239
pubmed: 28271076
Cancer Res Treat. 2017 Jan;49(1):29-36
pubmed: 27384155
PLoS One. 2012;7(3):e33411
pubmed: 22448244
Oncotarget. 2017 Mar 28;8(13):20706-20718
pubmed: 28157701
Oncoimmunology. 2014 Dec 13;3(9):e955691
pubmed: 25941621
Oncoimmunology. 2021 Oct 29;10(1):1995999
pubmed: 34745769
Eur J Pharmacol. 2019 Sep 15;859:172541
pubmed: 31319067
Int Immunol. 2019 Mar 28;31(4):187-198
pubmed: 30508092
Int J Radiat Oncol Biol Phys. 2015 Oct 1;93(2):454-64
pubmed: 26383681
Lancet Oncol. 2014 Feb;15(2):184-90
pubmed: 24440473
Dis Colon Rectum. 2020 Jun;63(6):758-768
pubmed: 32384406
Medicine (Baltimore). 2017 Mar;96(13):e6487
pubmed: 28353591
Radiat Res. 2014 Jun;181(6):641-9
pubmed: 24844651
Jpn J Cancer Res. 1996 Jan;87(1):78-85
pubmed: 8609053
Am J Cancer Res. 2019 Apr 01;9(4):800-815
pubmed: 31106005
J Surg Res. 2021 Dec;268:465-473
pubmed: 34418650
JAMA Oncol. 2015 Dec;1(9):1325-32
pubmed: 26270858
BMJ. 2005 Jun 4;330(7503):1304-5
pubmed: 15849206
Biochim Biophys Acta. 2014 Aug;1846(1):121-9
pubmed: 24797212
Clin Cancer Res. 2013 Dec 15;19(24):6741-50
pubmed: 24141625
J Clin Med. 2021 Jun 28;10(13):
pubmed: 34203451
Cancer Discov. 2012 Sep;2(9):778-90
pubmed: 22926251
Cells. 2021 Feb 06;10(2):
pubmed: 33562088
J Clin Oncol. 2018 Jun 1;36(16):1611-1618
pubmed: 29437535
Radiother Oncol. 2020 Oct;151:95-105
pubmed: 32592892
Cancer Sci. 2020 Nov;111(11):4012-4020
pubmed: 32794612
J Immunol. 2012 Jul 15;189(2):558-66
pubmed: 22685313
Int J Cancer. 2020 Oct 1;147(7):1904-1916
pubmed: 32196659
Lancet Oncol. 2014 Jun;15(7):700-12
pubmed: 24831977
Lancet Oncol. 2017 Jul;18(7):895-903
pubmed: 28551359
Ann Oncol. 2016 Dec;27(12):2184-2195
pubmed: 27681864
Dis Colon Rectum. 2020 Jul;63(7):918-926
pubmed: 32229782
Cancer Prev Res (Phila). 2014 Sep;7(9):867-85
pubmed: 24985407
Hepatology. 2009 Sep;50(3):799-807
pubmed: 19551844
J Cell Mol Med. 2018 Aug;22(8):3825-3836
pubmed: 29726618
Cancer Res. 2014 Oct 1;74(19):5458-68
pubmed: 25274032
Nat Rev Cancer. 2005 Nov;5(11):867-75
pubmed: 16327765
J Immunol. 2020 May 1;204(9):2575-2588
pubmed: 32221038
Cancer Epidemiol. 2019 Oct;62:101587
pubmed: 31491730
Cancer Med. 2013 Feb;2(1):99-107
pubmed: 24133632
BMC Cancer. 2020 May 12;20(1):411
pubmed: 32397971
Cancer Lett. 2015 Dec 1;369(1):192-201
pubmed: 26304716
J Immunol. 2009 Jan 1;182(1):240-9
pubmed: 19109155
Oncology (Williston Park). 2012 Aug;26(8):730-5, 741
pubmed: 22957406
J Immunol. 2005 Jun 15;174(12):7516-23
pubmed: 15944250
Cancer Immunol Res. 2015 Jun;3(6):610-9
pubmed: 25701325
Proc Natl Acad Sci U S A. 2015 Feb 10;112(6):1809-14
pubmed: 25624476