Effects of metronidazole on colorectal cancer occurrence and colorectal cancer liver metastases by regulating Fusobacterium nucleatum in mice.
CT26 cells
DNA relative expression
F. nucleatum
colorectal cancer
colorectal cancer liver metastases
gut microbiota
metronidazole
Journal
Immunity, inflammation and disease
ISSN: 2050-4527
Titre abrégé: Immun Inflamm Dis
Pays: England
ID NLM: 101635460
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
revised:
13
10
2023
received:
14
06
2023
accepted:
16
10
2023
medline:
30
11
2023
pubmed:
29
11
2023
entrez:
29
11
2023
Statut:
ppublish
Résumé
Colorectal cancer (CRC) represents a leading cause of cancer-related deaths. Metronidazole (MNZ) is exceedingly implicated in CRC. This study explored the roles of MNZ in mouse CRC occurrence and liver metastasis (CRLM). Male BALB/c nude mice were subjected to CRC and CRLM modeling, orally administration with MNZ (1 g/L) 1 week before modeling, and disease activity index (DAI) evaluation. Fresh stool and anal swab samples were collected on the morning of the 28th day after modeling. The relative expression of Fusobacterium nucleatum (F. nucleatum) DNA was assessed by quantitative polymerase chain reaction. After euthanasia, tumor tissues and liver tissues were separated and the tumor volume and weight change were measured. The liver tissues were stained with hematoxylin-eosin to quantitatively analyze the metastatic liver nodules. Malignant tumor biomarker Ki67 protein levels in liver tissues/DNA from stool samples were detected by immunohistochemistry/high-throughput 16S rRNA gene sequencing. Bioinformatics analysis was performed on the raw sequence data to analyze microbial community richness (Chao1 index, ACE index) and microbial community diversity (Shannon index). The DAI and F. nucleatum DNA relative expression in feces and anal swabs of the CRC and CRLM groups were raised and repressed after MNZ intervention. MNZ repressed tumor occurrence and growth in mice to a certain extent, alleviated CRLM malignant degree (reduced liver metastases and Ki67-positive cell density/number), and suppressed CRC liver metastasis by regulating intestinal flora structure, which affected the intestinal characteristic flora of CRC and CRLM mice. MNZ suppressed CRC occurrence and CRLM in mice by regulating intestinal F. nucleatum.
Identifiants
pubmed: 38018574
doi: 10.1002/iid3.1067
pmc: PMC10683560
doi:
Substances chimiques
Metronidazole
140QMO216E
Ki-67 Antigen
0
RNA, Ribosomal, 16S
0
DNA
9007-49-2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1067Subventions
Organisme : Science and Technology Fund Project of Guizhou Health Care Commission
ID : gzwjkj2019-1-123
Informations de copyright
© 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.
Références
J Med Chem. 1990 Apr;33(4):1200-6
pubmed: 2157011
Lancet. 2019 Oct 19;394(10207):1467-1480
pubmed: 31631858
Eur Rev Med Pharmacol Sci. 2019 Jan;23(1):397-401
pubmed: 30657582
Cancers (Basel). 2022 Apr 28;14(9):
pubmed: 35565327
Am J Chin Med. 2021;49(4):805-828
pubmed: 33827382
Cancer Med. 2023 Jan;12(1):513-524
pubmed: 35607944
Cell Rep. 2021 Oct 26;37(4):109886
pubmed: 34706245
Oral Dis. 2020 Jan;26(1):122-130
pubmed: 31710746
EMBO Rep. 2019 Apr;20(4):
pubmed: 30833345
Eur J Cancer. 2020 Nov;140:105-118
pubmed: 33075623
PLoS One. 2020 May 22;15(5):e0232905
pubmed: 32442163
J Cell Physiol. 2019 Mar;234(3):2337-2344
pubmed: 30191984
J Exp Clin Cancer Res. 2021 Feb 1;40(1):52
pubmed: 33526059
Int J Mol Sci. 2021 Jul 27;22(15):
pubmed: 34360768
World J Gastroenterol. 2014 May 28;20(20):6113-22
pubmed: 24876733
ACS Infect Dis. 2021 Aug 13;7(8):2285-2298
pubmed: 34259502
Oncology. 2020;98(9):593-602
pubmed: 32604093
J Gastroenterol Hepatol. 2021 Jun;36(6):1508-1517
pubmed: 33295040
Biomolecules. 2021 Dec 18;11(12):
pubmed: 34944546
BMC Complement Altern Med. 2017 Dec 02;17(1):516
pubmed: 29197355
Cell Host Microbe. 2023 May 10;31(5):781-797.e9
pubmed: 37130518
Front Cell Infect Microbiol. 2020 Aug 07;10:400
pubmed: 32850497
Science. 2017 Dec 15;358(6369):1443-1448
pubmed: 29170280
Nat Rev Gastroenterol Hepatol. 2019 Nov;16(11):690-704
pubmed: 31554963
Cancer Biother Radiopharm. 2013 Oct;28(8):615-22
pubmed: 23777253
J Nutr Biochem. 2018 Nov;61:111-128
pubmed: 30196243
JAMA. 2003 Mar 12;289(10):1288-96
pubmed: 12633191
Cancer Med. 2021 May;10(10):3358-3372
pubmed: 33838016
J Clin Invest. 2022 Mar 15;132(6):
pubmed: 35113809
Lancet. 2014 Apr 26;383(9927):1490-1502
pubmed: 24225001
Front Genet. 2021 Feb 01;12:608313
pubmed: 33597969
Food Chem Toxicol. 2020 Apr;138:111237
pubmed: 32145354
Int J Cancer. 2019 Jun 15;144(12):3086-3098
pubmed: 30515752
FEBS Open Bio. 2019 Jul;9(7):1305-1314
pubmed: 31141316
Hum Exp Toxicol. 2020 Jun;39(6):834-847
pubmed: 31997653
World J Gastroenterol. 2016 Jan 14;22(2):501-18
pubmed: 26811603
World J Gastroenterol. 2017 Sep 14;23(34):6261-6272
pubmed: 28974892
J Pediatr Gastroenterol Nutr. 2021 Jul 1;73(1):23-29
pubmed: 33633081
Ann Afr Med. 2019 Jul-Sep;18(3):121-126
pubmed: 31417011
Cancer Cell. 2012 Apr 17;21(4):504-16
pubmed: 22516259
BMC Microbiol. 2022 Dec 29;22(1):321
pubmed: 36581836
Cancer Sci. 2021 Nov;112(11):4470-4477
pubmed: 34464993
Vaccines (Basel). 2023 Feb 23;11(3):
pubmed: 36992108
World J Gastroenterol. 2016 Jan 21;22(3):1078-87
pubmed: 26811648
Eur J Clin Microbiol Infect Dis. 2019 Oct;38(10):1891-1899
pubmed: 31367996
Cell Host Microbe. 2023 Jan 11;31(1):141-145
pubmed: 36634619
J Oncol. 2022 Jun 11;2022:9690401
pubmed: 35726221
Biomed Pharmacother. 2021 Mar;135:111206
pubmed: 33418307
J Transl Med. 2022 Apr 21;20(1):178
pubmed: 35449107
Int J Mol Sci. 2022 Feb 18;23(4):
pubmed: 35216396
Gut Microbes. 2020 May 3;11(3):511-525
pubmed: 31910722
Phytomedicine. 2023 Jan;108:154524
pubmed: 36375238
Molecules. 2021 Aug 02;26(15):
pubmed: 34361836