Effect Of Low-Temperature Plasma On Metastatic Processes Of Solid Tumors In Vitro

Abstract

Cancer metastasis is one of the leading causes of mortality in patients with solid tumors [1]. The complex metastatic process involves cell migration and remodeling of the tumor microenvironment, among other factors. The intrinsic limitations of conventional cancer therapies for solid tumors have motivated the development and application of alternative technologies. In this context, the use of low-temperature plasmas (LTPs) has been explored in vitro and in vivo with considerable success against a variety of cancers [2,3]. However, whether LTP can inhibit or promote metastasis of solid tumors is unknown. The aim of this study is to investigate the effect of direct and indirect LTP treatments on metastatic processes of glioblastoma, adenocarcinoma and pancreatic cancers. For this purpose, we used a 3-dimensional multicellular spheroid model that mimics the pathophysiological conditions and complex architecture of solid tumors [4]. Spheroids were generated using glioblastoma U87, U251 and LN229, adenocarcinoma MDA-MB-231 and human pancreatic carcinoma MIA PaCa-2 cell lines and glioblastoma primary cells GR04, GR08 and GR15. Direct and indirect plasma treatments were administered to spheroids in PBS solution using the COST plasma jet and kINPen IND. We used live cell imaging to assess cytotoxicity and spheroid morphology, microscopy to monitor cell migration and immunohistochemistry to assess extracellular matrix remodeling in response to direct and indirect LTP treatment. Our study provides insight on the application of LTP treatment as potential cancer therapy for solid tumors.

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LN229 spheroids in PBS: (a) untreated control, directly treated with (b) kINPen IND or (c) COST jet. Outer border: total spheroid area; dark filled area: proliferative core (live cells); grey dots: dead cells.