Vitexin inhibits renal cell carcinoma progression by targeting Galectin-1-mediated glycolytic metabolism.
Vitexin, a natural flavonoid compound, has shown anti-tumor effects, but its mechanism in Renal cell carcinoma (RCC) remains unclear. Galectin-1, a β-galactoside-binding lectin, promotes tumor progression through metabolic reprogramming.
This study examined whether vitexin has antitumor activity against RCC by targeting Galectin-1 and its downstream metabolic pathways.
Human RCC cell lines (A498 and ACHN) were treated with vitexin to assess cell viability, apoptosis, cell cycle, migration, and invasion. Galectin-1 expression was manipulated through overexpression and knockdown approaches. Transcriptomic and metabolomic profiling were performed to identify pathway alterations. Glycolytic metabolism was evaluated using ATP measurements, glucose consumption, lactate production assays. The in vivo efficacy was validated using A498 xenograft models in nude mice.
Vitexin inhibited RCC cell proliferation, while significantly downregulating Galectin-1 expression. Furthermore, vitexin treatment caused cell cycle arrest, promoted apoptosis, and suppressed colony formation, migration, and invasion. Galectin-1 overexpression rescued vitexin-induced growth inhibition and reduced apoptosis. Transcriptomic analysis revealed that Galectin-1 modulation affected PI3K-AKT pathways, with significant alterations in glycolytic genes (SLC2A1, HK1, HK2, PFKM, PFKP, LDHB). Metabolomic profiling showed Galectin-1-dependent reprogramming of oxidative phosphorylation and energy metabolism. In addition, galectin-1 knockdown impaired glycolytic flux, reduced ATP production, glucose consumption, and lactate secretion. Conversely, Galectin-1 overexpression enhanced these metabolic parameters and activated PI3K/AKT signaling, counteracting vitexin's metabolic suppression. In vivo, vitexin significantly inhibited tumor growth, downregulated Galectin-1 and PI3K/AKT signaling, reduced cell proliferation, and increased TUNEL-positive apoptotic cells.
Vitexin exerts anti-tumor effects in RCC by targeting Galectin-1, which disrupts glycolytic metabolism through PI3K/AKT signaling inhibition. These findings suggest that the vitexin targeting Galectin-1 represents a potential therapeutic strategy for treating RCC.
This study examined whether vitexin has antitumor activity against RCC by targeting Galectin-1 and its downstream metabolic pathways.
Human RCC cell lines (A498 and ACHN) were treated with vitexin to assess cell viability, apoptosis, cell cycle, migration, and invasion. Galectin-1 expression was manipulated through overexpression and knockdown approaches. Transcriptomic and metabolomic profiling were performed to identify pathway alterations. Glycolytic metabolism was evaluated using ATP measurements, glucose consumption, lactate production assays. The in vivo efficacy was validated using A498 xenograft models in nude mice.
Vitexin inhibited RCC cell proliferation, while significantly downregulating Galectin-1 expression. Furthermore, vitexin treatment caused cell cycle arrest, promoted apoptosis, and suppressed colony formation, migration, and invasion. Galectin-1 overexpression rescued vitexin-induced growth inhibition and reduced apoptosis. Transcriptomic analysis revealed that Galectin-1 modulation affected PI3K-AKT pathways, with significant alterations in glycolytic genes (SLC2A1, HK1, HK2, PFKM, PFKP, LDHB). Metabolomic profiling showed Galectin-1-dependent reprogramming of oxidative phosphorylation and energy metabolism. In addition, galectin-1 knockdown impaired glycolytic flux, reduced ATP production, glucose consumption, and lactate secretion. Conversely, Galectin-1 overexpression enhanced these metabolic parameters and activated PI3K/AKT signaling, counteracting vitexin's metabolic suppression. In vivo, vitexin significantly inhibited tumor growth, downregulated Galectin-1 and PI3K/AKT signaling, reduced cell proliferation, and increased TUNEL-positive apoptotic cells.
Vitexin exerts anti-tumor effects in RCC by targeting Galectin-1, which disrupts glycolytic metabolism through PI3K/AKT signaling inhibition. These findings suggest that the vitexin targeting Galectin-1 represents a potential therapeutic strategy for treating RCC.