Novel nano-platinum induces autophagy through dual pathways in the treatment of osteosarcoma in cell lines with different P53 expression patterns

The enhancement of platinum-based chemotherapeutic agents utilizing nanotechnology holds promise for improving the prognosis of osteosarcoma chemotherapy in the context of a focus on autophagy. This study aims to examine the correlation and potential mechanisms between novel nano-platinum (Nano-Pt), osteosarcoma, and autophagy at both the cellular and animal levels. This study investigated the impact of Nano-Pt on the malignant biological behavior of three osteosarcoma cell lines (MG-63, U2-OS, and 143B), which was subsequently confirmed through animal experimentation. Furthermore, the association between Nano-Pt and PI3K/AKT/mTOR, P53/mTOR, and autophagy pathways was examined in diverse osteosarcoma cells. Utilizing confocal microscopy and transmission electron microscopy, it was observed that Nano-Pt possesses the capability to enter osteosarcoma cells. It was demonstrated that Nano-Pt exhibits a substantial inhibitory impact on proliferation, migration, and clone formation, while concurrently inducing apoptosis. The anticancer efficacy of Nano-Pt in vivo, as well as its lower normal cellular and tissue toxicity, were further substantiated through animal experimentation. Through rescue experiments based on autophagy inhibitor (3-MA) and mTOR agonist (MHY1485), mRFP-GFP-LC3 autophagic flux detection, TEM autophagosome observation, autophagy and apoptosis-related Western blotting, and apoptosis flow cytometry confirmed the ability of Nano-Pt to promote autophagy and apoptosis. It was revealed that Nano-Pt promotes autophagy through different pathways in cells with different P53 expression patterns. Nano-Pt demonstrated inhibition of cell proliferation and migration, as well as promotion of apoptosis, in all three types of osteosarcoma cells. Moreover, Nano-Pt induced autophagy mediated by the PI3K/AKT/mTOR pathway in MG-63 cells, while activating autophagy mediated by the P53/mTOR pathway and PI3K/AKT/mTOR pathway in U2-OS and 143B cells.