Bufalin Targets CENPA-modulated Glycolysis via PI3K/AKT in Hepatocellular Carcinoma: A Bioinformatics, In Vitro and Preliminary In Vivo Evidence

作者：Saeed MM, Wei T, Iqbal MK, Jabbar S, Akram R, Bai C, Liu Y, Cui X · 发表于：Molecular and cellular endocrinology · 年份：2026 · DOI：10.1016/j.mce.2026.112907

BACKGROUND: Hepatocellular carcinoma (HCC) remains a substantial therapeutic challenge because of its high recurrence rate and resistance to conventional therapies, necessitating the exploration of novel approaches. A crucial aspect of cancer metabolism is the Warburg effect, which promotes tumor progression by increasing glycolysis. Bufalin is a key component of a natural product derived from the venom of toads (Bufo gargarizans), which has anticancer properties. Centromeric protein A (CENPA) has been reported to play a significant role in the progression of many cancers, including HCC. However, the effect of bufalin on CENPA expression via the PI3K/AKT signaling pathway remains to be elucidated. The current study aimed to fill this gap, which could lead to a novel therapeutic approach for HCC. METHODS: Bioinformatics tools were used to identify CENPA as a key glycolysis-related gene (GRG) linked with poor prognosis in patients with HCC. In vitro experiments, such as Cell Counting Kit-8 (CCK-8), wound healing, Transwell migration, RT-qPCR, Western blotting (WB), and transfection assays, were used to assess the impact of bufalin on CENPA expression in HCC cell lines. Additionally, molecular docking was employed to calculate the binding energy between bufalin and CENPA. Preliminary xenograft immunohistochemistry extended these findings in vivo. RESULTS: Bioinformatics analysis identified CENPA as a glycolysis-related prognostic gene in HCC. Bufalin reduced CENPA mRNA and pro...