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

Background: 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. Methods: 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. Results: 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 (3MA) 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. Conclusions: 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.