Liu Wei formula ameliorates EGFR-induced malignant glioma progression by regulating EGFR/PI3K/AKT pathway and T-cell...

Gliomas, common malignant intracranial tumors, are associated with a poor prognosis and pose a significant threat to human health. Liu Wei formula (LWF), a century-old herbal formula developed by Tai Kang Gu Lou Hospital of Nanjing University of Chinese Medicine, shows clinical efficacy against glioma. However, the fundamental molecular mechanisms and pathways through which LWF exerts its therapeutic effects remain largely unclear.

A LUC-GL261 mouse model was established to assess the in vivo efficacy of LWF. Network pharmacology analysis was used to identify target enrichment regions between active components of LWF and glioma cells. Western blot (WB) was performed to evaluate the impact of LWF on human EGFR, phosphatidylinositol 3-kinase (PI3K), P-PI3K, protein kinase B (AKT), and P-AKT expression. Network pharmacology and differential gene analysis were used to identify differentially expressed genes and key signaling pathways, and quantitative real-time PCR (qPCR) was used to validate changes in target genes in EGFR-related pathways affected by the administration of LWF. Flow cytometry was used to detect changes in the proportion of T cells in tumor lymph nodes of mice treated with LWF. Surface plasmon resonance (SPR), molecular docking, and WB were performed to explore the functional ingredients of LWF. Additional clinical research is needed to clarify the clinical efficacy of LWF.

LWF significantly suppressed tumor growth in mice. Network pharmacology and experimental validation revealed inhibition of the EGFR/PI3K/AKT pathway and downregulation of related genes. Flow cytometry analysis revealed a significant increase in the proportion of CD8⁺T cells in mouse lymph nodes after LWF treatment. Baicalin and luteolin, as active ingredients of LWF, play important roles in the treatment of glioma. LWF demonstrated durable antitumor activity in glioma patients and improved clinical symptoms, including dizziness, headache, and nausea.

The above results indicate that LWF, through its main antitumor components baicalin and luteolin, suppresses malignant progression of EGFR-induced glioma by blocking the EGFR/PI3K/AKT pathway and enhancing T-cell expansion and function. This study offers a dual contribution: it presents clinical candidates for EGFR-driven glioma therapy and introduces a novel framework for determining the functional basis of LWFs.