Elucidating the Mechanism of Agrimonolide in Treating Colon Cancer Based on Network Pharmacology.
PI3K/AKT/mTOR pathway
agrimonolide
colon cancer
in vivo
network pharmacology
Journal
Drug design, development and therapy
ISSN: 1177-8881
Titre abrégé: Drug Des Devel Ther
Pays: New Zealand
ID NLM: 101475745
Informations de publication
Date de publication:
2023
2023
Historique:
received:
03
04
2023
accepted:
16
06
2023
medline:
4
8
2023
pubmed:
3
8
2023
entrez:
3
8
2023
Statut:
epublish
Résumé
This study reported the efficacy and underlying mechanism of agrimonolide (AM) in treating colon cancer. Colon cancer-AM-related targets were screened from online database. AM targets for colon cancer were identified by Venn diagram. Main molecular function, biological process, cellular component and pathways associated with AM targets for colon cancer were analyzed by GO and KEGG enrichment analysis. Relationship of the 10 core targets of AM for colon cancer with the top 15 BP and KEGG pathways was analyzed by Cytoscape software. A "component-target-pathway" network was constructed to select the hub genes of AM for colon cancer. AM effects on colon cancer cell viability, proliferation, invasion, migration and apoptosis were researched by CCK-8, colony formation, Transwell invasion, wound healing and flow cytometry assays. Tumor-bearing nude mice models were constructed and given AM treatment. Hub gene expression in cells/tissues was detected by Western blot. A total of 107 targets were selected as AM targets for colon cancer. The 10 core targets were related to the top 15 biological process terms and KEGG pathways. PI3K, AKT and mTOR were selected as the hub genes of AM for colon cancer. AM weakened colon cell proliferation, invasion, migration and apoptosis inhibition, and suppressed colon cell in vivo growth. AM up-regulated Caspase-3 and BAX proteins, down-regulated C-Myc, Cyclin D1 and BCL-2 proteins, and inactivated the PI3K/AKT/mTOR pathway both in vitro and in vivo. AM suppressed colon cancer progression through inactivating the PI3K/AKT/mTOR pathway. It may be useful for colon cancer treatment.
Identifiants
pubmed: 37533972
doi: 10.2147/DDDT.S409530
pii: 409530
pmc: PMC10390720
doi:
Substances chimiques
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
agrimonolide
21499-24-1
Phosphatidylinositol 3-Kinases
EC 2.7.1.-
TOR Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2209-2222Informations de copyright
© 2023 Yu and Gai.
Déclaration de conflit d'intérêts
The authors declare that they have no conflicts of interest in this work.
Références
JAMA Oncol. 2022 May 1;8(5):760-769
pubmed: 35238866
Mol Med Rep. 2021 Oct;24(4):
pubmed: 34414457
PLoS One. 2021 Oct 19;16(10):e0258817
pubmed: 34665844
Molecules. 2022 Jan 28;27(3):
pubmed: 35164185
Semin Cancer Biol. 2022 Oct;85:69-94
pubmed: 34175443
Phytomedicine. 2016 Jul 15;23(8):846-55
pubmed: 27288920
Theranostics. 2021 Jan 1;11(5):2201-2217
pubmed: 33500720
Front Pharmacol. 2017 Jan 11;7:513
pubmed: 28119605
Front Immunol. 2022 Nov 22;13:1032314
pubmed: 36483562
Phytomedicine. 2022 Jul;101:154102
pubmed: 35526323
Nat Biotechnol. 2007 Oct;25(10):1110-1
pubmed: 17921993
Int J Mol Sci. 2021 Nov 27;22(23):
pubmed: 34884633
J Cell Mol Med. 2021 Nov;25(22):10575-10590
pubmed: 34655278
Genes (Basel). 2019 Mar 22;10(3):
pubmed: 30909496
Curr Cancer Drug Targets. 2022;22(11):889-903
pubmed: 35762543
Mutat Res. 2012 Jun 1;734(1-2):30-40
pubmed: 22531693
Biomolecules. 2021 Oct 27;11(11):
pubmed: 34827586
J Clin Gastroenterol. 2006 Aug;40(7):592-5
pubmed: 16917399
Int J Cancer. 2018 Aug 15;143(4):921-930
pubmed: 29524226
Curr Drug Targets. 2019;20(12):1217-1226
pubmed: 31215384
Int J Mol Sci. 2019 May 11;20(9):
pubmed: 31083525
Front Pharmacol. 2022 Jun 14;13:862966
pubmed: 35774597
Food Funct. 2016 Nov 9;7(11):4605-4613
pubmed: 27747355
Nat Rev Clin Oncol. 2018 May;15(5):273-291
pubmed: 29508857
Mol Med Rep. 2019 Sep;20(3):2783-2795
pubmed: 31524255
J Biochem Mol Toxicol. 2023 May;37(5):e23313
pubmed: 36683349
Clin Colorectal Cancer. 2014 Mar;13(1):5-13
pubmed: 24361441
Pharmacy (Basel). 2022 Aug 05;10(4):
pubmed: 36005935
Cancer Rep (Hoboken). 2021 Jun;4(3):e1353
pubmed: 33655717
BMC Complement Med Ther. 2020 Jul 6;20(1):209
pubmed: 32631392
Molecules. 2020 May 31;25(11):
pubmed: 32486502
BMC Complement Med Ther. 2021 Sep 3;21(1):222
pubmed: 34479552
Biochem Biophys Res Commun. 2022 Feb 26;594:93-100
pubmed: 35078113