Cold Physical Plasma-Treated Buffered Saline Solution as Effective Agent Against Pancreatic Cancer Cells

Background: Cold physical plasma has been suggested as a new anticancer tool recently. However, direct use of plasma is limited to visible tumors and in some clinical situations, is not feasible. This includes repetitive treatment of peritoneal metastases, which commonly occur in advanced gastrointestinal cancer and in pancreatic cancer in particular. In case of diffuse intraperitoneal metastatic spread, Hyperthermic Intraperitoneal Intraoperative Chemotherapy (HIPEC) is used as a therapeutic approach. Plasma-treated solutions may combine non-toxic characteristics with the anticancer effects of HIPEC. Previous work has provided evidence for an anticancer efficacy of plasma-treated cell culture medium but the clinical relevance of such an approach is low due to its complex formulation and lack of medical accreditation. Objective: Plasma-treated Phosphate-Buffered Saline (PBS), which closely resembles medically certified solutions, was investigated for its cytotoxic effect on 2D monolayer murine pancreatic cancer cells in vitro. Methods: Toxicity studies of primary murine fibroblasts, PDA6606 murine pancreatic cancer cells, and COLO 357 human pancreatic cancer cells exposed to plasma-treated PBS were performed. Results: Plasma-treated PBS significantly decreased cancer cell metabolisms and proliferation whereas plasma-treated Dulbecco's Modified Eagle Medium had no effect. Moreover, tumor cell growth attenuation was significantly higher when compared to syngeneic primary murine fibroblasts. Both results were confirmed in a human pancreatic cancer cell line. Finally, plasma-treated PBS also decreased the size of pancreatic tumors in a three-dimensional manner, and induction of apoptosis was found to be responsible for all anticancer effects identified. Conclusion: Plasma-treated PBS inhibited cell growth in 2D and 3D models of cancer. These results may help facilitate the development of new plasma-derived anticancer agent with clinical relevance in the future.