Apatinib-Induced Protective Autophagy And Apoptosis Through The AKT-mTOR Pathway In Anaplastic Thyroid Cancer

Background: Anaplastic thyroid carcinoma(ATC)is one of the most lethal human malignancies,and there is no efficient method to slow its process.ATC is prone to hematogenous metastasis.Apatinib,an inhibitor of vascular endothelial growth factor receptor-2,has been shown to promote anticancer action across a wide range of malignancies,including gastric,lung,and breast cancers.Our previous study showed that apatinib increases apoptosis of anaplastic thyroid carcinoma(ATC),but the direct functional mechanism of tumour lethality mediated by apatinib is largely unknown.Our study aims to investigate the relationship between autophagy and apoptosis induced by apatinib in ATC cells.Methods: In this study,we explored the effects and mechanisms of Apatinib on tumor growth and angiogenesis in vitro and in vivo in ATC cells.We used CCK-8 assays and colony formation assay to analyze the effects of Apatinib on the proliferation of ATC cell lines.The effects of apoptosis of Apatinib on ATC cells were assessed by flow cytometry.Confocal microscopy and Electron microscopy were used to analyze the effect of antiangiogenesis of Apatinib.CQ,chloroquine and ATG7 si RNA were used to detect the the relationship between autophagy and apoptosis induced by apatinib in ATC cells.In addition,Western blot was administered to detect the expression of protein level.Results:(1)This study shows that apatinib can inhibit the viability of ATC cells.(2)Increasing the level of apatinib increases the formation of autophagosomes.(3)Apatinib can induce apoptosis in undifferentiated thyroid cells.(4)AKT / m TOR signaling pathway affects apatinib-induced autophagy and apoptosis.(5)Inhibition of aptatinib-induced autophagy enhances apatinib-induced apoptosis in ATC cells.(6)CQ combined with apatinib can inhibit tumors more effectively in vivo experiments..Conclusion: Our results demonstrated that Apatinib could induce autophagy and apoptosis through the AKT/m TOR pathway in ATC cells and that autophagy inhibition by CQ and ATG 7si RNA could significantly enhance the anti-cancer effect of apatinib.ATC patients might benefit from the new anticancer drug,and molecular targeted treatment in combination with autophagy inhibitors shows promise as a treatment improvement.