Journal
REDOX BIOLOGY
Volume 61, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.redox.2023.102647
Keywords
Inspiratory hyperoxia; Acid -base hemostasis; Lung cancer; Monocarboxylate transporter 1
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The effects of 60% oxygen exposure on the pH of lung cancer cells were evaluated in this study. The results showed that hyperoxia exposure reduced intracellular pH, leading to a decrease in the proliferation, invasion, and epithelial-to-mesenchymal transition of lung cancer cells. MCT1 was found to mediate intracellular lactate accumulation and acidification of the cells under hyperoxic conditions.
The perils and promises of inspiratory hyperoxia (IH) in oncology are still controversial, especially for patients with lung cancer. Increasing evidence shows that hyperoxia exposure is relevant to the tumor microenvironment. However, the detailed role of IH on the acid-base homeostasis of lung cancer cells remains unclear. In this study, the effects of 60% oxygen exposure on intra- and extracellular pH were systematically evaluated in H1299 and A549 cells. Our data indicate that hyperoxia exposure reduces intracellular pH, which might be expected to reduce the proliferation, invasion, and epithelial-to-mesenchymal transition of lung cancer cells. RNA sequencing, Western blot, and PCR analysis reveal that monocarboxylate transporter 1 (MCT1) mediates intracellular lactate accumulation and intracellular acidification of H1299 and A549 cells at 60% oxygen exposure. In vivo studies further demonstrate that MCT1 knockdown dramatically reduces lung cancer growth, invasion, and metastasis. The results of luciferase and ChIP-qPCR assays further confirm that MYC is a transcription factor of MCT1, and PCR and Western blot assays confirm that MYC is downregulated under hyperoxic conditions. Collectively, our data reveal that hyperoxia can suppress the MYC/MCT1 axis and cause the accumulation of lactate and intracellular acidification, thereby retarding tumor growth and metastasis.
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