The Application of the Cold Plasma-Stimulated Medium in Cancer Treatment Open Access
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Over past several years, the cold plasma, an ionized, near room temperature gas has shown its promising application in cancer treatment. The cold plasma shows a significantly anti-cancer capacity over dozens of cancer cell lines in vitro and subcutaneous tumors in mice. Different from conventional anti-cancer tools and drugs, the cold plasma is a selective anti-cancer tool. Recently, the cold plasma-stimulated medium (PSM) has shown its remarkable anti-cancer capacity as strong as the direct cold plasma irradiation. Because PSM is independent of the cold plasma device, PSM has noticeable advantage in the cancer treatment when a cold plasma device is not available or when the plasma jet cannot touch the tumor tissues in depth. Since PSM is a novel anti-cancer tool, many key problems in this field have not been resolved. In this dissertation, a novel model based on the different expression of aquaporins between cancer cells and normal cells has been proposed to explain the selective anti-cancer capacity of cold plasma. In addition, the role of medium in the anti-cancer application of PSM has been comprehensively investigated. FBS in medium not only significantly consumes the plasma-originated reactive species such H2O2 but also contribute to the degradation of PSM during the storage. Several principles have been demonstrated to optimize the anti-tumor capacity of PSM on glioblastoma cells and breast cancer cells. Specifically, a larger well, a closer gap between plasma source and medium, and a smaller volume of medium produce a stronger anti-cancer PSM. Compared with RNS, H2O2 in PSM is more likely to be the main anti-cancer species. Moreover, it is found that cysteine and methionine are main components in DMEM contributing to the degradation of PSM during the storage over a wide temperature range. The cold plasma-stimulated cysteine/methionine-free DMEM or 3-Nitro-L-tyrosine-rich DMEM will remain its anti-cancer capacity over a wide temperature range for at least three days. Furthermore, it is found that adding 20 mM of lysine into DMEM significantly enhances the anti-glioblastoma capacity of PSM even the cell confluence is high. Ultimately, I first discover that cancer cells consume the cold plasma-originated reactive species such as H2O2 with different speeds. Glioblastoma cells consume H2O2 significantly faster than breast cancer cells, which may be due to the distinct expression levels of aquaporins in different cancer cells. In short, my study builds a solid foundation for the application of PSM and provides important clues to understand the anti-cancer capacity of the cold plasma treatment.