Sophoricoside Inhibited Glioblastoma Cell Progression Through Activated AMP‐Activated Protein Kinase (AMPK)

ABSTRACT Glioblastoma (GBM) is the most common malignant primary brain tumor, with a mean survival of less than 2 years. Unique brain structures and the microenvironment, including blood−brain barriers, put great challenges on clinical drug development. Sophoricoside (Sop), an isoflavone glycoside isolated from seeds of Sophora japonica L., is one of the active constituents of traditional Chinese medicine and found to inhibit the bioactivity of cytokines (e.g., interleukin‐5) and inflammatory responses, as well as to attenuate glucose and lipid metabolism in related diseases. However, the effects of Sop on cancer progression have not been systemically investigated. In this study, we performed a comprehensive investigation of Sop's function in GBM using colony formation and Transwell assays in vitro, along with subcutaneous xenograft tumor analysis in vivo. We employed RNA sequencing and bioinformatics analysis in conjunction with Western blotting (WB) and reverse transcription‐quantitative polymerase chain reaction (RT‐PCR) to explore the underlying mechanism. Our results demonstrated that Sop suppressed U251 cell proliferation and metastasis in vitro and inhibited the tumorigenic behavior of U251 cells in vivo. Further investigations revealed a positive correlation between the levels of activated AMP‐activated protein kinase (AMPK) and Sop treatment; notably the application of the AMPK inhibitor, compound C (CC), abolished inhibitory effects of Sop on the malignant phenotype of U251 cells. These findings suggest the potential application of Sop in GBM treatment and highlight opportunities for the development of new therapeutic strategies.