Title:Cold Physical Plasma-Treated Buffered Saline Solution as Effective Agent Against Pancreatic Cancer Cells
Volume: 18
Issue: 6
Author(s): Sander Bekeschus*, André Käding, Tim Schröder, Kristian Wende, Christine Hackbarth, Kim R. Liedtke, Julia van der Linde, Thomas von Woedtke, Claus-Dieter Heidecke and Lars-Ivo Partecke
Affiliation:
- Leibniz-Institute for Plasma Science and Technology (INP Greifswald), ZIK plasmatis, Felix-Hausdorff-Str. 2, 17489 Greifswald,Germany
Keywords:
Apoptosis, cold physical plasma, HIPEC, human, murine, PBS, phosphate-buffered saline, plasma medicine.
Abstract: 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.