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. 2023 Jul 27:17:2209-2222.
doi: 10.2147/DDDT.S409530. eCollection 2023.

Elucidating the Mechanism of Agrimonolide in Treating Colon Cancer Based on Network Pharmacology

Lei Yu  1 , Yun Gai  1
Affiliations

Elucidating the Mechanism of Agrimonolide in Treating Colon Cancer Based on Network Pharmacology

Lei Yu et al. Drug Des Devel Ther. .

Abstract

Purpose: This study reported the efficacy and underlying mechanism of agrimonolide (AM) in treating colon cancer. VSports手机版.

Methods: 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 V体育安卓版. Hub gene expression in cells/tissues was detected by Western blot. .

Results: 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 V体育ios版. .

Conclusion: AM suppressed colon cancer progression through inactivating the PI3K/AKT/mTOR pathway. It may be useful for colon cancer treatment VSports最新版本. .

Keywords: PI3K/AKT/mTOR pathway; agrimonolide; colon cancer; in vivo; network pharmacology V体育平台登录. .

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Conflict of interest statement

The authors declare that they have no conflicts of interest in this work.

Figures (V体育官网入口)

Figure 1
Figure 1
Targets of AM for colon cancer. (A) A total of 107 AM targets for colon cancer were screened by Venn diagram. (B) PPI network analysis of AM targets for colon cancer was performed by using the String database. The green nodes in the middle represented the larger degree values.
Figure 2
Figure 2
GO and KEGG analysis of AM targets for colon cancer. (A-C) The top 15 significant enriched terms by GO functional enrichment analysis were shown at MF level, BP level and CC level. (D) The top 15 significant KEGG pathways were exhibited.
Figure 3
Figure 3
Relationship of AM core targets for colon cancer with the top 15 BP and KEGG pathways. (A) Core network of the top 10 core targets of AM for colon cancer. (B) Relationship of the core network with the top 15 BP terms in GO enrichment analysis. (C) Relationship of the core network with the top 15 KEGG pathways.
Figure 4
Figure 4
Core hub genes of AM for colon cancer. Triangle nodes represented BP terms; prismatic nodes represented KEGG terms; circle nodes represented genes and dark purple nodes indicated the higher degree values.
Figure 5
Figure 5
AM inhibited the proliferation, invasion and migration but induced the apoptosis of colon cells. (A) CCK-8 assay revealed that the IC50 value of HCT-116 cells to AM was 29.05 μM. (B-F) CCK-8 assay, colony formation assay, Transwell invasion assay, wound healing assay and flow cytometry implied the suppression role of AM on the viability, proliferation, invasion and migration, but the induction role on the apoptosis of HCT-116 cells. (G) Western blot implied the promotion of AM on the expression of Caspase-3 and BAX proteins, but the inhibition on the expression of C-Myc, Cyclin D1 and BCL-2 proteins in HCT-116 cells. *P < 0.05 and **P < 0.01 vs HCT-116 cells treated by 0 μM AM.
Figure 6
Figure 6
AM inactivated the PI3K/AKT/mTOR pathway in colon cells. *P < 0.05 and **P < 0.01 vs HCT-116 cells treated by 0 μM AM.
Figure 7
Figure 7
AM weakened colon cell growth and inactivated the PI3K/AKT/mTOR pathway in vivo. (A and B) Tumor-bearing nude mice were subjected to AM treatment (AM group) or not (Control group). AM treatment suppressed the in vivo growth of HCT-116 cells, as evidenced by the lower tumor volume and weight in the AM group. (C and D) AM treatment increased the expression of Caspase-3 and BAX proteins, reduced the expression of C-Myc, Cyclin D1 and BCL-2 proteins, and inactivated the PI3K /AKT/mTOR pathway in xenograft tumor tissues. *P < 0.05 and **P < 0.01 vs Control group.
Figure 8
Figure 8
The work flow of the present study.
See this image and copyright information in PMC

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