Network Pharmacology and Molecular Docking Analysis on the Mechanism of Hedyotis Diffusa in Overcoming Resistance in EGFR Mutant Cell Line HCC827-GR and Its Experimental Verification

Hedyotis diffusa is a Chinese herbal medicine commonly used to treat various forms of inflammation and tumors. In order to further study the molecular mechanism of its treatment of lung cancer and its possible active components.

Active compounds were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform with criteria of drug-likeness ≥ 0.18 and oral bioavailability ≥ 30%. Lung cancer-related genes were retrieved from Online Mendelian Inheritance in Man, Therapeutic Target Database, and GeneCards， using the search term' Lung Cancer'. The protein-protein interaction networks were constructed using the STRING database, and enrichment analyses for the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology were performed via the DAVID platform. Molecular docking was conducted via the CB-Dock2 platform. In the cell experiment, we induced drug resistance in HCC827 cells by gradually increasing Gefitinib concentration. We evaluated the effect of Hedyotis diffusa extract on the proliferation, migration, and invasion of the drug-resistant cell lines.

The active components of Hedyotis diffusa exhibit strong interactions with numerous important targets in lung cancer, particularly key molecules such as AKT and EGFR. Cell experiments showed that Hedyotis diffusa significantly inhibited the migration and invasion of HCC827/GR cells and decreased the expression of EMT-related marker proteins.

Based on this study, Hedyotis diffusa can significantly inhibit the migration and invasion of EGFR-mutant, drug-resistant lung adenocarcinoma cells. This finding provides a mechanistic basis for overcoming acquired resistance to EGFR-TKIs and lays an experimental foundation for developing combination treatment strategies for lung cancer.

Hedyotis diffusa can modulate the IGF-1R/PI3K/AKT-EMT pathway by targeting Akt, EGFR, and other key proteins, thereby intervening in acquired resistance to EGFR-TKIs in EGFR-mutant lung adenocarcinoma.