PI3K/mTOR inhibitors promote G6PD autophagic degradation and exacerbate oxidative stress damage to radiosensitize small cell lung cancer.

ABSTRACT: Our previous study revealed that PI3K/AKT/mTOR signaling was associated with SCLC radioresistance. SBC2 cells were used as primary radioresistance models, while H446 cells were continuously exposed to ionizing radiation (IR) to develop acquired radioresistance. Cell viability and apoptosis assays were used to investigate synergistic effects of BEZ235/GSK2126458 and IR in vitro, while immunoblotting, metabolite quantitative analysis and bioinformatic analyses were utilized to explore the underlying mechanism. Both genetically engineered mouse models (GEMM) and subcutaneous tumor models were used to confirm the synergistic effect in vivo. Key molecules of PI3K/AKT/mTOR signaling were upregulated after IR, which was correlated with primary radioresistance, and they were more expressed in acqu

SUBMITTER: Deng H 

PROVIDER: S-EPMC10558571 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature