Hypoxia is a critical characteristic of solid
tumors with respect to
cancer cell survival, angiogenesis, and
metastasis. Hyperoxic treatment has been attempted to reverse
hypoxia by enhancing the amount of dissolved
oxygen in the plasma. In this study, we evaluated the effects of normobaric
hyperoxia on the progression of
lung cancer to determine whether
oxygen toxicity can be used in
cancer therapy. Following a tail vein injection of the
Lewis lung carcinoma cells, C57BL/6J mice were exposed to a 24-h normobaric
hyperoxia/normoxia cycle for two weeks. In addition, A549
lung cancer cells were incubated in a normobaric
hyperoxia chamber for a 24-h period. As a result, the size and number of
tumors in the lung decreased significantly with exposure to normobaric
hyperoxia in the mouse model. Cell viability, colony-forming ability, migration, and invasion all decreased significantly in A549 cells exposed to normobaric
hyperoxia and the normal control group exposed to normobaric
hyperoxia showed no significant damage. Oxidative stress was more prominent with exposure to normobaric
hyperoxia in
cancer cells. A549 cells exposed to normobaric
hyperoxia showed a significantly higher cell apoptosis ratio compared with A549 cells without normobaric
hyperoxia exposure and normal human lung cells (BEAS-2B cells). The Bax/Bcl-2
mRNA expression ratio also increased significantly. Changes in the key regulators of apoptosis were similar between in vivo and in vitro conditions. The p-ERK level decreased, while the p-JNK level increased, after normobaric
hyperoxia exposure in A549 cells. This study demonstrated the role of normobaric
hyperoxia in inhibiting
lung cancer. Normal tissue and cells showed no significant hyperoxic damage in our experimental setting. The anti-
tumor effect of normobaric
hyperoxia may due to the increased
reactive oxygen species activity and apoptosis, which is related to the
mitogen-activated protein kinase pathway. Impact statement Normobaric
hyperoxia (NBO) is a feasible
therapy for
cancer with a low complication rate. Although NBO may be beneficial in
cancer treatment, very few studies have been conducted; thus, the evidence is thin. This is the first study to clearly demonstrate morphological changes in
lung cancer with NBO exposure and to investigate the underlying mechanisms both in vivo and in vitro. This study will arouse interest in NBO treatment and promote further research.