Oxidative stress mediated by nitrogen at elevated pressure inhibits non-small cell lung cancer growth.

Purpose/Aim: High pressures of gases such as nitrogen enhance production of singlet oxygen. Therefore, we hypothesized that growth of non-small cell lung cancer (NSCLC) A549 cells and a human-derived NSCLC explant could be inhibited by an oxidative stress mechanism using high-pressure nitrogen.

MATERIALS AND METHODS: Growth of human NSCLC explants and A549 cells in Matrigel were assessed after implantation into nude mice who were exposed to elevated pressures.

RESULTS: Subcutaneous implant growth of NSCLC in nude mice was inhibited by a daily 78-minute protocol using nitrogen/oxygen breathing mixture such that at the maximum pressure of 2.78 atmospheres over ambient, mice breathed oxygen at normal atmospheric pressure. In vivo growth inhibition of A549 cells by high-pressure nitrogen could be abrogated in subcutaneous Matrigel implants when supplemented with 10-mM N-acetylcysteine as an antioxidant. Ex vivo A549 cell exposures exhibited elevated singlet oxygen production, and reactive oxygen species were produced for up to 4 hours after short-term high-pressure nitrogen exposure.

CONCLUSIONS: This pilot study demonstrates that elevated normoxic nitrogen pressure can exacerbate oxidative stress in NSCLC to inhibit growth.