Exploring the Anti-Osteosarcoma Effects and Mechanisms of Rhizoma Paridis Total Saponins Based on SLC7A11-Mediated Ferroptosis

Abstract

Background: Rhizoma paridis total saponins (RPTS) constitute the principal bioactive compound in Rhizoma paridis, demonstrating anticancer properties in various tumor types. However, its mechanism of action in osteosarcoma (OS) remains unclear. This study aimed to elucidate the role of RPTS on OS cells and tumor progression, focusing on its modulation of Solute Carrier Family 7 Member 11 (SLC7A11)-mediated ferroptosis. Methods: 143B cells were cultured in vitro, and assays were conducted to assess cell viability, proliferation, apoptosis, migration, intracellular reactive oxygen species (ROS) levels, mitochondrial membrane potential, ferroptosis-related proteins, and epithelial-mesenchymal transition (EMT) markers. Nude mice were subcutaneously injected with 143B cells to establish an osteosarcoma mouse model. Tumor volume and weight were recorded. EMT process markers and ferroptosis-related protein expression were detected in the tumor tissues. Results: In vitro experiments revealed that RPTS significantly inhibited cell viability, proliferation, and migration and promoted apoptosis (p < 0.05). Moreover, RPTS increased intracellular ROS accumulation and reduced mitochondrial membrane potential (p < 0.05). RPTS inhibited the EMT process, upregulated p53 protein expression, and downregulated glutathione peroxidase 4 (GPX4) and SLC7A11 expression in 143B cells (p < 0.05). Overexpression of SLC7A11 rescued RPTS-induced ROS accumulation and ferroptosis in 143B cells (p < 0.05), and significantly increased RPTS-induced inhibition of cell proliferation and migration (p < 0.05). In vivo, RPTS significantly suppressed tumor growth and EMT markers, upregulated p53 protein expression and decreased GPX4 and SLC7A11 protein expressions (p < 0.05). Conclusion: RPTS induced ferroptosis in osteosarcoma by inhibiting SLC7A11 expression and regulated cell viability, proliferation, apoptosis, migration, and EMT processes, demonstrating an inhibitory effect on osteosarcoma.