Hyperbaric oxygen rescues lung cancer cells from chemical hypoxia-induced low differentiation and apoptosis resistance

Abstract

Hypoxia induces vigorous growth and a higher malignant phenotype in solid tumors. Hyperoxic treatment using hyperbaric oxygen (HBO) has previously been shown as a highly effective method to attenuate hypoxia. We aimed to investigate the effect of HBO on hypoxia-induced malignancy of lung cancer cells. Cobalt chloride (CoCl2) was used to induce chemical hypoxia in lung cancer cell line A549. Hypoxic inducible factor-1α (HIF-1α) expression, lactate dehydrogenase (LDH) activity, migration and invasion capacity, expression profiles of epithelial-mesenchymal transition (EMT) markers and apoptotic markers were assessed in CoCl2-treated A549 cells, with or without HBO treatment. Chemical hypoxia caused by CoCl2 resulted in high LDH activity, increased migration and invasion, decreased E-cadherin/N-cadherin ratio, enhanced EMT phenotype, higher Bcl-2/Bax ratio and elevated GRP78 expression. HBO treatment could significantly attenuate hypoxia-induced LDH activity, migration and invasion, restore hypoxia-reduced E-cadherin/N-cadherin ratio and EMT phenotype, as well as hypoxia-induced Bcl-2/Bax ratio, and repress GRP78 expression. HBO could serve as a reliable adjuvant treatment targeting the hypoxia microenvironment in solid tumors.