Network pharmacology and anticancer mechanism study of Dendrobium nobile dendrobine in the treatment of colorectal cancer

Abstract

Objective: This study aims to explore the potential targets and anticancer mechanisms of dendrobine from Dendrobium nobile in the treatment of colorectal cancer through network pharmacology, and to experimentally validate its specific effects.

Methods: Initially, potential targets of dendrobine were identified using the ITCM Traditional Chinese Medicine database, while colorectal cancer-related genes were obtained from the NCBI Gene database, with the intersection of these datasets taken for further analysis. Functional enrichment analysis was conducted using the Metascape database, and a protein-protein interaction (PPI) network was constructed. Additionally, cell culture, cell proliferation assays, and wound healing assays were performed. The Wnt/β-catenin and NF-κB/COX-2/PGE₂ signaling pathways were analyzed using PCR and Western blot experiments.

Results: The PPI network constructed from 152 intersecting genes revealed that these genes play crucial roles in processes such as cell proliferation, apoptosis, and signal transduction. Cell-based assays demonstrated that dendrobine significantly inhibits the proliferation and migration of colorectal cancer cells. Furthermore, PCR and Western blot results indicated that dendrobine suppresses colorectal cancer cell proliferation and migration by modulating the Wnt/β-catenin and NF-κB/COX-2/PGE₂ signaling pathways.

Conclusion: Dendrobine exhibits significant anticancer potential against colorectal cancer by regulating the Wnt/β-catenin and NF-κB/COX-2/PGE₂ signaling pathways, providing a theoretical foundation and experimental evidence for its therapeutic application in colorectal cancer.

Keywords: Colorectal cancer; Dendrobium nobile dendrobine; NF-κB/COX-2/PGE2 signaling pathway; Network pharmacology; Wnt/β-catenin signaling pathway.

Fig. 1

The connectivity score heatmap of Dendrobium nobile dendrobine across various cell lines

Fig. 2

A volcano plot depicting the impact of Dendrobium nobile dendrobine on colorectal cancer cells

Fig. 3

A Venn diagram illustrating the overlap between Dendrobium nobile dendrobine and colorectal cancer-related genes

Fig. 4

The gene ontology (GO) functional enrichment analysis of Dendrobium nobile dendrobine in relation to colorectal cancer-associated genes. A The gene enrichment network, where nodes represent GO terms and different colors denote various functional categories. B The significance levels of the enriched GO terms, with color intensity indicating increasing levels of significance.)

Fig. 5

The heatmap of gene ontology (GO) functional enrichment analysis for Dendrobium nobile dendrobine in colorectal cancer-associated genes. A–C The enrichment significance under various GO functional categories, with color intensity from light to dark indicating increasing levels of significance.)

Fig. 6

The protein–protein interaction (PPI) network of Dendrobium nobile dendrobine in relation to colorectal cancer-associated genes. A The entire PPI network, with nodes representing genes and edges denoting interactions between them. B The gene clustering within various modules, where genes within each module demonstrate high levels of interaction.)

Fig. 7

The IC50 curve of Dendrobium nobile dendrobine on colorectal cancer cells

Fig. 8

The effect of Dendrobium nobile dendrobine on the proliferation of colorectal cancer cells: HT29 cells (A), SW480 cells (B)

Fig. 9

The effect of Dendrobium nobile dendrobine on the migration of colorectal cancer cells: HT29 cells (A), SW480 cells (B)

Fig. 10

The impact of Dendrobium nobile dendrobine on the expression of genes related to the Wnt/β-catenin signaling pathway in colorectal cancer cells. HT29 cells: β-catenin (A), c-myc (B), cyclin D1 (C); SW480 cells: β-catenin (D), c-myc (E), cyclin D1 (F)

Fig. 11

The impact of Dendrobium nobile dendrobine on the expression of genes related to the NF-κB/COX-2/PGE2 signaling pathway in colorectal cancer cells. HT29 cells: NF-κB (A), COX-2 (B), PGE2 (C); SW480 cells: NF-κB (D), COX-2 (E), PGE2 (F)

Fig. 12

The impact of Dendrobium nobile dendrobine on the expression of key proteins in the Wnt/β-catenin signaling pathway in colorectal cancer cells. HT29 cells: Western blot image of protein expression levels (A), bar graph of β-catenin protein expression (B), bar graph of c-myc protein expression (C), bar graph of cyclin D1 protein expression (D); SW480 cells: Western blot image of protein expression levels (E), bar graph of β-catenin protein expression (F), bar graph of c-myc protein expression (G), bar graph of cyclin D1 protein expression (H)

Fig. 13

The impact of Dendrobium nobile dendrobine on the expression of key proteins in the NF-κB/COX-2/PGE2 signaling pathway in colorectal cancer cells. HT29 cells: Western blot image of protein expression levels (A), bar graph of NF-κB protein expression (B), bar graph of COX-2 protein expression (C), bar graph of PGE2 protein expression (D); SW480 cells: Western blot image of protein expression levels (E), bar graph of NF-κB protein expression (F), bar graph of COX-2 protein expression (G), bar graph of PGE2 protein expression (H)