Plasma-activated media selectively induces apoptotic death via an orchestrated oxidative stress pathway in high-grade serous ovarian cancer cells.

Abstract

High-grade serous ovarian cancer (HGSOC) is the most common and aggressive type of ovarian cancer. Due to a lack of an early detection test and overt symptoms, many patients are diagnosed at a late stage where metastasis makes treatment very challenging. Furthermore, the current standard treatment for HGSOC patients, consisting of debulking surgery and platinum-taxane chemotherapy, reduces quality of life due to debilitating side-effects. Sadly, 80-90% of patients diagnosed with advanced stage ovarian cancer will die due to treatment resistance. As such, novel therapeutic strategies for HGSOC that are both more effective and less toxic are urgently required. Here we describe the assessment of cold atmospheric pressure (CAP) gas discharge technology as a novel treatment strategy in pre-clinical models of HGSOC. Plasma-activated media (PAM) was generated using cell growth media. HGSOC cell lines, patient ascites cells and primary tissue explants were tested for their response to PAM via analysis of cell viability, cell death and oxidative stress assays. Our data show that PAM treatment can be more effective than standard carboplatin chemotherapy at selectively targeting ovarian cancer cells in primary patient samples. Further, we also observed PAM to induce apoptosis in HGSOC cancer cell lines via induction of oxidative stress and mitochondrial-mediated apoptosis. These findings suggest that PAM is a viable therapeutic strategy to test in in vivo models of ovarian cancer, with a view to develop an intraperitoneal PAM-based therapy for HGSOC patients. Our studies validate the ability of PAM to selectively target tumour tissue and ascites cells. This work supports the development of PAM towards in vivo validation and translation into clinical practice.