1 Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, St. Paul's Hospital, College of Medicine, The Catholic University of Korea, Seoul 02559, Republic of Korea.
2 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon 21431, Republic of Korea.
Exp Biol Med (Maywood). 2018 May;243(9):739-748. doi: 10.1177/1535370218774737.
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.
缺氧是实体瘤中与癌细胞存活、血管生成和转移相关的一个关键特征。人们曾尝试通过增加血浆中溶解氧的含量来进行高氧治疗，以此来逆转缺氧。在这项研究中，我们评估了常压高氧对肺癌进展的影响，以确定氧毒性是否可用于癌症治疗。通过尾静脉注射 Lewis 肺癌细胞后，C57BL/6J 小鼠接受了两周的常压高氧/常氧循环暴露。此外，将 A549 肺癌细胞置于常压高氧室中孵育 24 小时。结果，在小鼠模型中，暴露于常压高氧可显著减小肿瘤的大小和数量。暴露于常压高氧的 A549 细胞的细胞活力、集落形成能力、迁移和侵袭能力均显著下降，而暴露于常压高氧的正常对照组未见明显损伤。氧化应激在接受常压高氧的癌细胞中更为明显。与未暴露于常压高氧的 A549 细胞和正常人肺细胞（BEAS-2B 细胞）相比，暴露于常压高氧的 A549 细胞的细胞凋亡比例明显更高。Bax/Bcl-2mRNA 表达比值也显著增加。在体内和体外条件下，凋亡关键调节剂的变化相似。A549 细胞暴露于常压高氧后，p-ERK 水平降低，而 p-JNK 水平升高。这项研究证明了常压高氧在抑制肺癌中的作用。在我们的实验设置中，正常组织和细胞没有表现出明显的高氧损伤。常压高氧的抗肿瘤作用可能归因于活性氧物种活性和凋亡的增加，这与丝裂原活化蛋白激酶途径有关。影响陈述常压高氧（NBO）是一种具有低并发症率的可行的癌症治疗方法。尽管 NBO 在癌症治疗中可能有益，但很少有研究；因此，证据不足。这是第一项明确显示 NBO 暴露后肺癌形态变化的研究，并在体内和体外均研究了潜在机制。这项研究将引起人们对 NBO 治疗的兴趣，并促进进一步的研究。
