Hyperbaric oxygen suppressed tumor progression through the improvement of tumor hypoxia and induction of tumor apoptosis in A549-cell-transferred lung cancer

Abstract

Tumor cells have long been recognized as a relative contraindication to hyperbaric oxygen treatment (HBOT) since HBOT might enhance progressive cancer growth. However, in an oxygen deficit condition, tumor cells are more progressive and can be metastatic. HBOT increasing in oxygen partial pressure may benefit tumor suppression. In this study, we investigated the effects of HBOT on solid tumors, such as lung cancer. Non-small cell human lung carcinoma A549-cell-transferred severe combined immunodeficiency mice (SCID) mice were selected as an in vivo model to detect the potential mechanism of HBOT in lung tumors. HBOT not only improved tumor hypoxia but also suppressed tumor growth in murine xenograft tumor models. Platelet endothelial cell adhesion molecule (PECAM-1/CD31) was significantly increased after HBOT. Immunostaining of cleaved caspase-3 was demonstrated and apoptotic tumor cells with nuclear debris were aggregated starting on the 14th-day after HBOT. In vitro, HBOT suppressed the growth of A549 cells in a time-dependent manner and immediately downregulated the expression of p53 protein after HBOT in A549 cells. Furthermore, HBOT-reduced p53 protein could be rescued by a proteasome degradation inhibitor, but not an autophagy inhibitor in A549 cells. Our results demonstrated that HBOT improved tissue angiogenesis, tumor hypoxia and increased tumor apoptosis to lung cancer cells in murine xenograft tumor models, through modifying the tumor hypoxic microenvironment. HBOT will merit further cancer therapy as an adjuvant treatment for solid tumors, such as lung cancer.

Hyperbaric oxygen therapy for healthy aging: From mechanisms to therapeutics

“…Thus, both the hyperoxia and pressure components of HBOT play an indispensable role in promoting angiogenesis. To date, numerous studies have reported the pro-angiogenesis effects of HBOT in different tissues with compromised blood perfusion such as skin [ [26] , [27] , [28] , [29] ], brain [ [30] , [31] , [32] ], penile [ 33 ], bone [ 34 ], and even tumor [ 35 , 36 ]. These results firmly establish the pro-angiogenesis effects of HBOT, implying its possible advantages in preventing age-related microcirculation impairments.…”

Hyperbaric Oxygen Therapy as a Complementary Treatment in Glioblastoma—A Scoping Review

“…Their results revealed that HBOT improves tissue angiogenesis and tumor hypoxia and increases tumor apoptosis by modifying the tumor's hypoxic microenvironment. The treatment also suppressed tumor growth in murine xenograft tumor models (57). This was the first study to demonstrate that HBOT immediately downregulated endogenous p53 protein, which rebounded to baseline after 20 h of treatment.…”

“…The anticancer effects of hyperoxia and its action mechanisms are mostly identified in mouse lung cancer (55,56). To detect the potential mechanism of HBOT in lung tumors, Chen et al (57) selected, as an in vivo model, non-small cell human lung carcinoma A549-cell-transferred severe-combined immunodeficiency mice (SCID). Their results revealed that HBOT improves tissue angiogenesis and tumor hypoxia and increases tumor apoptosis by modifying the tumor's hypoxic microenvironment.…”

The Role of Imaging Biomarkers to Guide Pharmacological Interventions Targeting Tumor Hypoxia

“…Another efficient method to increase tumor oxygenation is to provide a gas enriched in oxygen, for example 100% oxygen or carbogen (i.e., mixture of 95% O 2 and 5% CO 2 or 98% O 2 and 2% CO 2 ) (Siemann et al, 1977;Rojas et al, 1990;Falk et al, 1992;Grau et al, 1992;Horsman et al, 1994;Hoskin et al, 1997;Hill et al, 1998;Kaanders et al, 1998;Powell et al, 1999;Kaanders et al, 2002;Overgaard, 2007;Hoskin et al, 2009;Khan et al, 2009;Hoskin et al, 2010;Khan et al, 2010;Overgaard, 2011;Janssens et al, 2012;Thews and Vaupel, 2016;Song et al, 2021). Hyperbaric oxygen has also demonstrated a beneficial effect to reoxygenate tumors (Henk et al, 1977;Haffty et al, 1999;Becker et al, 2002;Thews and Vaupel, 2015;Chen et al, 2021). While breathing oxygen or carbogen is efficient in alleviating tumor hypoxia, some pharmacological approaches have led to a better response in sensitizing tumors to irradiation because they may act by several mechanisms including intrinsic radiosensitizing properties.…”