Title:Mechanisms Underlying the Therapeutic Effects of Banzhilian-Baihuasheshecao for Treating Pancreatic Ductal Adenocarcinoma Based on Bioinformatics Strategy
Volume: 21
Issue: 13
Author(s): Xianqiang Zhou and Tiansong Zhang*
Affiliation:
- Department of Pulmonary Diseases, Jing’an District Hospital of Traditional Chinese Medicine, Shanghai 200072, China
- Department of Traditional Chinese Medicine, Jing’an District Central Hospital Affiliated to Fudan University, Shanghai
200040, China
Keywords:
Banzhilian (BZL), Baihuasheshecao (BHSSC), pancreatic ductal adenocarcinoma (PDAC), network pharmacology, single-cell RNA sequencing, molecular docking.
Abstract:
Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of
cancer-related deaths. Banzhilian (BZL) and Baihuasheshecao (BHSSC) are classical Chinese herbs
used in tumor therapy. However, the underlying mechanisms of BZL-BHSSC in treating PDAC have
not been identified. Combining network pharmacology with single-cell RNA sequencing (scRNA-seq),
this study systematically explored the potential mechanisms of BZL-BHSSC in the treatment of PDAC.
Methods: The bioactive ingredients of BZL-BHSSC were screened from the Traditional Chinese
Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database, while the
PDAC-related datasets were obtained from the Gene Expression Omnibus (GEO) database. Based on
the dataset GSE62452, we adopted differential expression analysis and weighted gene co-expression
network analysis (WGCNA) to screen the signature genes of PDAC. To reveal the cell types of the
pharmacological targets of BZL-BHSSC against PDAC, we performed scRNA-seq analysis and
principal component analysis (PCA) on the dataset GSE111672. Molecular docking and immunohistochemical
staining were used to validate our initial results.
Results: We obtained 29 bioactive ingredients from BZL-BHSSC and screened 210 signature genes
of PDAC. Using network pharmacology, we identified 7 key therapeutic targets CDK1, MYC,
CCNB1, TOP2A, CLDN4, NUF2, and MET, revealing that baicalein, quercetin, and luteolin are core
components for the efficacy of BZL-BHSSC. The main signaling pathways involved in therapy were
the PI3K-AKT signaling pathway and the p53 signaling pathway. The molecular docking results
verified the strong binding activity (binding energy > -7 kJ/mol) between active ingredients and targets.
The scRNA-seq results informed that cells from 3 PDAC samples could aggregate into 19 clusters
and 3 cell types. The target genes were almost concentrated on the immune cells. Immunoinfiltration
analysis suggested that the expression of Macrophages M0 and Dendritic cells activated
was significantly upregulated in the PDAC group (p<0.001), while the opposite was true for B cells
naïve and T cells CD8 expression (p<0.05).
Conclusion: We concluded that BZL-BHSSC can improve the overall survival prognosis of PDAC
patients by interfering with the signature genes of PDAC through direct and indirect pathways and
improving immunity. Our study provides a basis for subsequent studies.
