Effect of Atmospheric-Pressure Plasmas on Drug Resistant Melanoma: The Challenges of Translating In vitro Outcomes into Animal Models

Abstract

Atmospheric-pressure plasmas (APs) have been identified as a promising cancer therapy that is able to preferentially kill neoplastic cells through apoptosis. In vitro studies suggest that AP-generated reactive oxygen species (ROS) are the principal triggers of apoptosis-related signaling cascades via oxidative stress and direct interference with DNA, proteins, and other cellular components. The results of this study corroborate an ROS-mediated mechanism of cancer cell death, with apoptosis in AP-treated Mel-007 melanoma cells inhibited by pretreatment of cells with the ROS scavenger N-acetylcysteine or the caspase inhibitor zVAD-fmk. In an effort to compare apoptosis mechanisms and evaluate the in vitro−in vivo correlation for AP-induced apoptosis, Mel-007 cells were injected subcutaneously into mice to form solid tumors and were treated with AP Histological assessment of tumors from control and AP-treated animals showed no significant difference in tumor volume, mitotic rate, or percentage of necrosis or multinucleate cells. These results vary from those of other studies of AP treatment of xenograft tumors in murine models, in which a decrease in tumor size and tumor volume were observed. These findings focus our attention on challenges associated with translating the in vitro results to corresponding in vivo outcomes, and highlight concerns about the applicability of mechanisms established in vitro to an intrinsically dynamic in vivo environment.