Aloin Induces Autophagy-related Apoptosis Through PI3K/AKT/mTOR Tor Pathway In Human Osteosarcoma Cells

Osteosarcoma is a common malignant tumor of bone and soft tissue in adolescents and the elderly.Due to its unique tumor biological behavior pattern,osteosarcoma usually generates multiple drug resistance and early lung metastasis,which brings challenges to its treatment.Autophagy is an important process for the circulation of metabolites,and also an important self-defense mechanism in tumor cells.Recent studies have shown that autophagy plays an important role in the drug resistance mechanism of osteosarcoma.A variety of targeted drugs for autophagy regulation have shown quite objective anti-tumor potential in vitro and in vivo.In this study,we found that Aloin can induce osteosarcoma apoptosis in a dose-dependent manner through detection of apoptosis-related proteins and flow cytometry,and screened out its possible effects on the PI3K/AKT pathway by means of network pharmacology.On this basis,it is further found that Aloin can increase the autophagy flux of osteosarcoma by down-regulating the PI3K/AKT pathway to achieve the effect of inhibiting osteosarcoma.In the study,it was found that Aloin promotes the autophagy of osteosarcoma cell lines HOS and MG63 in a dose-dependent manner,increases the expression levels of LC3 B,Beclin1,etc.,and promotes the formation of autophagosomes in osteosarcoma cells.Induction of autophagy inhibition by chloroquine can reverse the apoptosis-promoting effect and autophagy enhancement effect of aloin.The autophagy induced by starvation and rapamycin can significantly enhance the autophagic flux and apoptosis induced by aloin.Finally,in the nude mouse orthotopic xenogeneic osteosarcoma transplantation model,the therapeutic effect of aloin on osteosarcoma and its enhancement of autophagy on osteosarcoma cells in vivo and its regulatory effect on the PI3K/AKT/mTOR pathway were demonstrated.In summary,aloin can inhibit the proliferation of osteosarcoma by inhibiting the PI3K/AKT/mTOR pathway to increase autophagic flux and promote the apoptosis of osteosarcoma cells.