Suppression of Autophagy Sensitizes Osteosarcoma to mTOR Inhibition

Abstract

Aim Osteosarcoma is some major health problem. We intended to investigate the role of Rapamycin and autophagy inhibition in the treatment of osteosarcoma. Method We conducted a series of in vitro studies using two osteosarcoma cell lines. Using genetic and pharmaceutical interventions we studied whether combined autophagy inhibition could sensitize osteosarcoma sales to a Rapamycin treatment. Proliferation, innovation, migration, and colony formation assays were performed. Results Osteosarcoma cells had low basal autophagy levels. Inhibition of mTOR only demonstrated moderate effects but induced increased autophagy levels, indicating possible resistance mechanism. Inhibition of both autophagy and mTOR axis synergistically inhibited proliferation, migration, invasion, and colony formation of osteosarcoma cells. The combination therapy induced apoptosis, which could be restored in part by NEC1. Conclusion Increased autophagy level was responsible for compromised effect of mTOR inhibition in osteosarcoma. Combination therapy using rapamycin and chloroquine held promise to the development of novel mortality.