Docetaxel suppressed cell proliferation through Smad3/HIF-1α-mediated glycolysis in prostate cancer cells

• DOI: 10.1186/s12964-022-00950-z
• Publication Date: 2022-12-19T12:13:31Z
• Authors: Junming Peng; Zhijun He; Yeqing Yuan; Jing Xie; Yu Zhou; Baochun Guo; Jinan Guo
• Keywords: Anaerobic glycolysis

Abstract Background Tumor glycolysis is a critical event for tumor progression. Docetaxel widely used as first-line drug chemotherapy and shown to have survival advantage. However, the role of docetaxel in remained poorly understood. Methods The effect proliferation were performed by CCK-8, Western blotting, real-time PCR, glucose, lactate detection IHC. ChIP luciferase assay analyze mechanism on Smad3-mediated HIF-1α transactivity. Results In this study, we showed that treatment led significant inhibition cell prostate cancer cells through PFKP-mediated glycolysis. Addition lactate, production glycolysis, could reverse inhibitory proliferation. Further analysis has demonstrated phosphorylation Smad3 (Ser213) was drastically decreased response stimulation, leading reduce nuclear translocation. Luciferase Chromatin immunoprecipitation (ChIP) revealed inhibited binding promoter gene, suppressing transcriptional activation HIF-1α. Moreover, ectopic expression overcome its target gene PFKP caused treatment. Most importantly, endogenous regulated interacted with HIF-1α, interaction destroyed What’s more, both significantly reduced received vivo. Conclusion These findings extended essential targeting Smad3/HIF-1α signaling-mediated Warburg cells.