فهرست نشریات علمی دسترسی آزاد ایران

ColoRectal Cancer (CRC) is one of the most common malignancies, and the development of chemoresistance severely limits patient prognosis and survival. EleSclomol (ES), a copper chelator, has been reported to induce cuprotosis in cancer cells, while AstragaloSide IV (AS-IV), an active compound extracted from Astragalus membranaceus, exhibits potent anti-cancer effects. We investigated whether AS-IV enhances the anti-tumor efficacy of ES in oxaliplatin-resistant CRC cells. Oxaliplatin-resistant CRC cell lines (SW480-DR and SW620-DR) were treated with AS-IV, ES, or their combination. Cell proliferation and viability were evaluated using CCK-8, colony formation, and EdU assays. Tumor growth in vivo was assessed using a xenograft mouse model. Cancer cell stemness was examined via sphere formation assays, and expression of stemness markers and PI3K/AKT pathway proteins was analyzed by Western blotting. An AKT activator was applied to confirm the involvement of PI3K/AKT signaling. AS-IV significantly enhanced the inhibitory effect of ES on both in vitro and in vivo growth of oxaliplatin-resistant CRC cells. Combination treatment suppressed the sphere-forming ability and reduced the expression of stemness markers (CD133, CD44, Sox9, and Nanog). Furthermore, the combination inactivated PI3K/AKT signaling, while AKT activation partially reversed the observed anti-proliferative effects. These findings suggest that AS-IV synergistically enhances the anti-tumor activity of ES and reduces stemness in oxaliplatin-resistant CRC cells by inhibiting PI3K/AKT signaling, providing a potential therapeutic strategy to overcome chemoresistance in CRC.