# Mechanism of Curcumin in Inhibiting Proliferation of Head and Neck Squamous Cell Carcinoma: A Network Pharmacology and Cellular Experimental Study

**Authors:** Yating He, Yaqi Liao, Shizhen Fang, Ling Zhu, Zhang Zhao, Tingting Chen, Zhimin Zhang

PMC · DOI: 10.1155/bmri/4318115 · 2025-11-26

## TL;DR

This study explores how curcumin inhibits head and neck cancer growth using network analysis and lab experiments, identifying key molecular targets.

## Contribution

The study integrates network pharmacology and experimental validation to reveal curcumin's antitumor mechanism in HNSCC via the EGFR/STAT3 pathway.

## Key findings

- Curcumin inhibits cancer cell viability, invasion, and migration while promoting apoptosis in HNSCC cell lines.
- Curcumin downregulates EGFR/STAT3 expression at both mRNA and protein levels.
- RNA-seq analysis confirms suppression of the STAT pathway as a key anticancer mechanism.

## Abstract

Despite advances in cancer therapy, head and neck squamous cell carcinoma (HNSCC) remains a challenging malignancy with limited treatment options, prompting this investigation into curcumin′s antitumor mechanisms through integrated network pharmacology, molecular docking, and in vitro experiments. Our comprehensive analysis identified 34 potential targets, with AKT1, EGFR, and STAT3 emerging as core targets primarily involved in regulating proliferation, apoptosis, and migration via the EGFR/STAT3 pathway. Experimental validation demonstrated curcumin′s dose‐dependent inhibition of viability, invasion, and migration in FaDu and CAL 27 cells, while promoting apoptosis and downregulating EGFR/STAT3 expression at both mRNA and protein levels—effects that were synergistically enhanced when combined with AG490 inhibitor. RNA‐seq analysis further confirmed STAT pathway suppression as a key anticancer mechanism, collectively establishing curcumin′s therapeutic potential through EGFR/STAT3 axis modulation. Overall, these preliminary network pharmacology and in vitro experimental results suggest that curcumin is a potential therapeutic agent for HNSCC and is worthy of further study. This study provides a certain theoretical basis for future clinical exploration.

## Linked entities

- **Genes:** AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207], EGFR (epidermal growth factor receptor) [NCBI Gene 1956], STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774]
- **Chemicals:** curcumin (PubChem CID 969516), AG490 (PubChem CID 5328779)
- **Diseases:** head and neck squamous cell carcinoma (MONDO:0010150), HNSCC (MONDO:0010150)

## Full-text entities

- **Genes:** AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}
- **Diseases:** HNSCC (MESH:D000077195), cancer (MESH:D009369)
- **Chemicals:** Curcumin (MESH:D003474), AG490 (MESH:C095512)
- **Cell lines:** FaDu — Homo sapiens (Human), Hypopharyngeal squamous cell carcinoma, Cancer cell line (CVCL_1218), CAL 27 — Homo sapiens (Human), Tongue adenosquamous carcinoma, Cancer cell line (CVCL_1107)

## Figures

41 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12649822/full.md

---
Source: https://tomesphere.com/paper/PMC12649822