Abstract
Pancreatic cancer is associated with a high mortality rate. In advanced stage, patients often experience peritoneal carcinomatosis. Using a syngeneic murine pancreatic cancer cell tumor model, the effect of non-thermal plasma (NTP) on peritoneal metastatic lesions was studied. NTP generates reactive species of several kinds which have been proven to be of relevance in cancer. In vitro, exposure to both plasma and plasma-treated solution significantly decreased cell viability and proliferation of 6606PDA cancer cells, whereas mouse fibroblasts were less affected. Repeated intraperitoneal treatment of NTP-conditioned medium decreased tumor growth in vivo as determined by magnetic resonance imaging, leading to reduced tumor mass and improved median survival (61 vs 52 days; p < 0.024). Tumor nodes treated by NTP-conditioned medium demonstrated large areas of apoptosis with strongly inhibited cell proliferation. Contemporaneously, no systemic effects were found. Apoptosis was neither present in the liver nor in the gut. Also, the concentration of different cytokines in splenocytes or blood plasma as well as the distribution of various hematological parameters remained unchanged following treatment with NTP-conditioned medium. These results suggest an anticancer role of NTP-treated solutions with little to no systemic side effects being present, making NTP-treated solutions a potential complementary therapeutic option for advanced tumors.
Highlights
Pancreatic cancer causes over 330.000 deaths worldwide[1]
Oxidative action was shown by a strong increase of DCF fluorescence in the 6606PDA cells exposed to non-thermal plasma (NTP)-treated medium but not in the control samples (Fig. 1a) and not in fibroblasts either, even after addition of NTP-treated solution (Fig. 1b)
The cells’ metabolic activity, determined by Resazurin-degradation, decreased in a treatment time-dependent fashion in both cell types but 6606PDA cells showed a significantly stronger reduction following direct or indirect NTP-application compared to fibroblasts (10 s p < 0.001, 30 s p < 0.001, 60 s p < 0.0028; Fig. 1c,d)
Summary
Pancreatic cancer causes over 330.000 deaths worldwide[1]. Pancreatic ductal adenocarcinoma (PDA) is the most common entity of pancreatic malignancies, showing a very poor prognosis with a 5-year survival rate of about 6%2. We investigated the antitumor action of NTP-treated cell culture medium that was repeatedly applied to mice challenged with 6606PDA tumor cells, being in contact with both tumor nodes and physiological tissues. Innovative therapeutic approaches, such as this oxidative lavage, need to be tolerated well by the organism, and its benefits should outweigh the risks. With this in mind, we have investigated the efficacy of NTP-treated medium on cancer lesions and possible side effects in healthy tissues and whole blood. This study provides promising results and underlines an encouraging role of NTP-conditioned solutions in the multimodal treatment of malignancies in future therapies
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