Evaluation of the use of hyperbaric oxygen in suppression of hyper-proliferation in hypoxic NSCLC cells

Abstract

“Hyperbaric oxygen therapy (HBO)” is being researched as a potential adjuvant therapy for solid malignancies, such as NSCLC. It can reduce tumour hypoxia and has been found to slow tumour growth, stop dedifferentiation, and reduce apoptosis resistance in hypoxic NSCLC cells. Though HBO has shown promise in treating various cancers, more study is required to determine its precise mechanism of action in NSCLC. Examine the result of “hyperbaric oxygen therapy” on the proliferation of hypoxic “non-small cell lung cancer” cells. In addition, the “NSCLC cell lines A549 and H1299” were employed for the in vitro analysis of aerobic glycolysis. Warburg effect testing included glucose absorption, lactate, “adenosine triphosphate (ATP)”, and pyruvate measurements. Using a quantitative glycolytic flow model, we also analyzed the effect of HIF-1-induced genes on the flux of glucose metabolism. “Lewis lung carcinoma (LLC)” animal models in C57BL/6J mice were used to examine the development of lung tumours. The effects of pcDNA and HIF1A on glucose uptake, lactate production, pyruvate, and ATP levels were studied in “A549 and H1299 NSCLC cells”. The glucose absorption of A549 cells exhibited a gradual increase throughout the course of the experiment, but H1299 cells had a significant decrease in glucose absorption following HBO therapy. The levels of pyruvate were shown to be notably higher in the H1299 cell line, particularly under hypoxic conditions, and were observed to decrease in reaction to “hyperbaric oxygen therapy (HBO)”. In A549, the lactate content was more effective. After HBO treatment, glucose absorption was reduced while intracellular ATP levels were maintained. Overexpression of HIF-1a was able to counteract the effect of HBO on glycolytic gene expression. PFKP is a possible therapeutic target because HBO reduces the “Warburg effect in NSCLC cells” by downregulating “HIF-1”.