蛋氨酸缺失对脑胶质瘤细胞放射敏感性和辐射诱导免疫原性细胞死亡的影响和机制研究

Objective: To explore the effect and mechanism of methionine deprivation on radiosensitivity of GBM and radiation-induced ICD. Methods: GBM proliferation was detected by Edu assay, DNA damage was detected by immunofluorescence assay, cell clone survival rate was detected by cloning test, autophagy and mitochondrial autophagy were detected by electron microscope, apoptosis and CRT surface exposure were detected by flow cytometry. The content of ATP in the supernatant was detected by bioluminescence assay, the expression of autophagy-related proteins LC3B and p62 and the phosphorylation of ER stress pathway-related proteins PERK and IRE1 α were detected by Westernblot. Result: Under normoxic or hypoxic conditions, methionine deprivation inhibited the proliferation and promoted apoptosis of GBM cells, which increased the radiosensitivity of GBM, methionine deletion promoted autophagy formation and mitochondrial autophagy, up-regulated L3II expression and down-regulated p62 expression, combined with 3-MA further promoted GBM apoptosis and radiosensitivity to GBM. Methionine deprivation enhanced radiation-induced immunogenic cell death. Enhance the phosphorylation level of PERK and IRE1 α in endoplasmic reticulum stress related pathways. Conclusion: Methionine deprivation promotes the radiosensitivity of normoxic or hypoxic GBM, which may be related to its inhibition of GBM proliferation, promotion of apoptosis and induction of GBM autophagy. Methionine deprivationenhances the immunogenic cell death of IR to GBM through the phosphorylation of PERK and IER1 α in endoplasmic reticulum stress-related pathways.