Mechanistic study on cepharanthine enhancing temozolomide sensitivity in glioblastoma via PI3K-AKT signaling pathway

This study investigated the synergistic therapeutic effects and underlying mechanisms of Cepharanthine combined with Temozolomide in glioblastoma. In vitro experiments using U87 and U251 glioblastoma cell lines were divided into four groups: control, IC20 CEP, IC50 TMZ, and IC20 CEP+IC50 TMZ combination treatment. Cell viability, proliferative capacity, and apoptotic protein expression were assessed through CCK-8 assay, colony formation assay, Hoechst 33342 staining, and Western blot analysis. Network pharmacology predicted potential target pathways, with subsequent Western blot validation of phosphatidylinositol 3-kinase (PI3K), phosphorylated PI3K (p-PI3K), protein kinase B (AKT), and phosphorylated AKT (p-AKT) expression levels. For in vivo studies, a nude mouse xenograft model was established with four treatment groups: control (0 mg/kg), CEP (10 mg/kg), TMZ (20 mg/kg), and combination therapy, monitoring subcutaneous tumor growth, Ki67 expression, and histopathological changes. Results demonstrated that the CEP-TMZ combination significantly inhibited cell viability and promoted apoptosis in both U87 and U251 cell lines (PPP>0.05). In vivo, the combination group exhibited markedly slower tumor growth and reduced Ki67 positivity (P<0.01) without significant toxicity. In conclusion, CEP enhances TMZ sensitivity in glioblastoma by inhibiting the PI3K-AKT signaling pathway, demonstrating synergistic potential that may provide an experimental basis for clinical combination therapy.