Background The lack of knowledge about the effect of inspiratory hyperoxia (IH) on the lung-specific tumor microenvironment and progression of lung cancer has attracted considerable attention.Methods The effects of different oxygenation parameters on the proliferation, apoptosis, invasion and migration of lung cancer cells were systematically evaluated in vitro and in vivo, including CCK-8, transwell and metastasis models. Mechanistically, transcriptome, proteome and metabolome analysis were

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... bined to reveal the effects of IH on the malignant phenotype of lung cancer cell. Luciferase reporter analysis, Western blot, RNA immunoprecipitation and immunohistochemical staining were performed to examine the detailed regulatory mechanism of IH regulating metabolic reprogramming of lung cancer cells.Results Our results reveal that IH treatment (60% O2, 6h/day) not only has no tumor progression-promoting effects, but also suppresses lung cancer metastasis and promotes long-term survival. MYC/SLC1A5-induced metabolic reprogramming and glutamine addiction serves as a new mechanism that drives lung cancer metastasis, which can be significantly suppressed by IH.Conclusion MYC/SLC1A5-induced metabolic reprogramming and glutamine addiction is a new mechanism that drives lung cancer metastasis, which can be significantly suppressed by IH treatment. These findings are relevant to the debate on the perils, promises and antitumor effect of IH, especially for patients with lung cancer.