Identification of Molecular Targets and Potential Mechanisms of Yinchen Wuling San Against Head and Neck Squamous Cell Carcinoma by Network Pharmacology and Molecular Docking

Abstract

Head and neck squamous cell carcinoma (HNSCC) represents one of the most malignant and heterogeneous tumors, and the patients have low 5-year survival. Traditional Chinese medicine (TCM) has been demonstrated as an effective complementary and/or alternative therapy for advanced malignancies including HNSCC. It has been noted that several herbs that are used for preparing Yinchen Wuling San (YWLS) have anti-tumor activities, whereas their mechanisms of action remain elusive. In this study, network pharmacology and molecular docking studies were employed to explore the underlying mechanisms of action of YWLS against HNSCC. The 58 active ingredients from six herbs used for YWLS and their 506 potential targets were screened from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) and SwissTargetPrediction database. A total of 2,173 targets associated with HNSCC were mainly identified from the DisGeNET and GeneCards databases. An active components-targets-disease network was constructed in the Cytoscape. Top 20 hub targets, such as AKT1, EGFR, TNF, ESR1, SRC, HSP90AA1, MAPK3, ERBB2, and CCND1, were identified by a degree in the protein–protein interaction (PPI) network. Gene functional enrichment analysis showed that PI3K-AKT, MAPK, Ras, TNF, and EGFR were the main signaling pathways of YWLS in treating HNSCC. There were 48 intersected targets such as EGFR, AKT1, and TNF that were associated with patients’ outcomes by the univariate Cox analysis, and most of them had increased expression in the tumor as compared to normal tissues. The area under curves of receiver operating characteristic indicated their diagnostic potential. Inhibition of these survival-related targets and/or combination with EGFR or AKT inhibitors were promising therapeutic options in HNSCC. The partial active components of YWLS exhibited good binding with the hub targets, and ADME analysis further evaluated the drug-likeness of the active components. These compounds and targets identified in this study might provide novel treatment strategies for HNSCC patients, and the subsequent work is essential to verify the underlying mechanisms of YWLS against HNSCC.

Preliminary investigation of the anti‐colon cancer activity of cucurbitacin C from cucumber: A network pharmacological study and experimental validation

“…The resulting protein–protein interaction (PPI) network was visualized using Cytoscape software (version 3.9.1). To identify densely connected modules in the network, the molecular complex detection plugin was employed (Zhang et al., 2022). Furthermore, the CytoNCA plugin was used to calculate the node with the highest degree, indicating its importance in the network (Tang et al., 2015).…”

Network pharmacology: an efficient but underutilized approach in oral, head and neck cancer therapy—a review

“…In both studies, the PI3K-Akt signaling pathway was recognized as a crucial pathway influenced by bioactive compounds present in these remedies. Moreover, an NP study of Yinchen Wuling San, a complex medical prescription comprising six medicinal plants used for cancer treatment, revealed that the genes TNF, AKT1, and EGFR are targeted by the bioactive compounds of Yinchen Wuling San against HNSCC (Zhang et al, 2022). The gene targets obtained through NP could be further validated through molecular docking and other in silico experiments to confirm the effects of bioactive compounds on these targets.…”

“…YinchenWuling San (YWLS), comprising of six herbal ingredients, is another potential alternative for HNSCC therapy. However, the active components and antitumor mechanisms of YWLS require further investigation (Zhang et al, 2022).…”