Abstract 2839: Antitumor activity on colorectal and pancreatic tumors of a new strategy based on ROS generation by non-thermal plasma
Authors: Vandamme Marc , Brullé Laura , Ries Delphine , Robert Eric , Sarron Vanessa , Dozias Sébastien , Lerondel Stéphanie , Pouvesle Jean-Michel , Pape Alain Le 
Published: August 2012

Background. Local treatments of tumors are mainly based on surgical resection and/or treatment such as photodynamic therapy (PDT) or ionizing radiation (IR). Action mechanisms of IR and PDT are based on the generation of ROS in the vicinity of the cells. In this context, cold or Non Thermal Plasma (NTP), a new technology which can generate in situ ROS, is currently under investigations. NTP is a cold (&lt;40°C) ionized gas (air or noble gas) thank to an electric discharge. It contains free charges (electrons, ions), free radicals and excited molecules. NTP can be generated at the end of a catheter (plasma jet) allowing a local treatment that is compatible with usual endoscopes for dysplasia or non resecable tumors. Previous studies have shown an in vitro antitumor activity of NTP on various cells lines and in vivo on subcutaneous xenografts. The aim of this work was to assess the antitumor potential of fibred NTP when applied directly on in situ orthotopic human pancreatic or colorectal carcinoma xenografts. Methods. For in vitro experiments, HCT116-Luc and Mia Paca-Luc cells were seeded in 24-well plate and then treated with a plasma jet device called plasma gun. The effects on cells were assessed by bioluminescence imaging (BLI). For in vivo experiments, HCT116-Luc cells were xenografted in the caecum wall of nude mice and tumors were treated by a single NTP exposure 7 days post-induction. Concerning pancreatic tumors, MIA PaCa2-Luc cells were injected in the pancreas head and NTP treatments were started 4 days after implantation. Two others exposures were performed on D14 and D24. For both models, tumor growth was monitored by BLI once a week. Results and Discussion. NTP treatment showed a significant antitumor effect on HCT116 and Mia Paca cells in vitro and in vivo. In vitro plasma induced a decrease of BLI resulting from a massive cell death. Localized treatments of tumor using plasma gun induced significant tumor stabilization. On colorectal tumors, a BLI difference of 90% between treated and CTRL tumors were observed at D22. This effect was confirmed by tumor weight measurement. Moreover, a significant metastasis decrease was observed. Similar results were observed on pancreatic tumors with also a stabilization of tumor growth and a BLI decrease following each treatment leading finally at D36 to a significant difference of tumor volume (84%). Comparison of NTP with the references drug of these pathologies is ongoing. The results obtained on two different tumor types show the potential antitumor activity of NTP on implanted small tumors. These effects were linked to a high rate generation of ROS in the vicinity of tumors, inducing lethal DNA damages, a multiphase cell cycle arrest and finally apoptosis. Such results demonstrate the interest of NTP for treatment of dysplasia and non-resecable tumors that could be associated to real time per operative near infrared fluorescence imaging via fibro/coelioscopy.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2839. doi:1538-7445.AM2012-2839