Hypoxia-triggered autophagy modulates cisplatin resistance in non-small cell lung Cancer via EIF2AK3-dependent PI3K/AKT signaling and mTOR-independent mechanisms.

ABSTRACT: Chemoresistance in non-small-cell lung cancer (NSCLC) remains a significant clinical challenge, often exacerbated by the tumor microenvironment's hypoxic conditions. Hypoxia has been implicated in promoting autophagy and contributing to chemoresistance, yet the underlying mechanisms are not fully elucidated. In this study, we investigated the role of EIF2AK3 in hypoxia-induced autophagy and cisplatin (DDP) resistance in NSCLC cells. Our findings demonstrated that hypoxia upregulates EIF2AK3 expression, leading to enhanced autophagy, as indicated by increased LC3-II/I ratios. Pharmacological inhibition of autophagy with 3-MA effectively reversed hypoxia-induced DDP resistance. Mechanistically, hypoxia-activated EIF2AK3 enhanced autophagy and decreased DDP sensitivity in NSCLC cells via PI3K

SUBMITTER: Fu J 

PROVIDER: S-EPMC12827477 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature