In vitro antitumor activity of plasma Gun

International audienceOur group has recently showed a marked antitumor effect of DBD plasma treatment in vivo on U87 glioma bearing mice. Beside these results in vivo, various studies have showed an antitumor effect of plasma treatment on various cancer cells lines in vitro by apoptosis induction using DBD or plasma jet. In our lab, development of a plasma jet so called plasma gun lead to new very interesting perspectives in a context of tumor treatment via small catheter. The main goal of this work was to investigate the in vitro cells sensitivity to plasma and major cells mechanisms induce by plasma gun treatment. Experiments were performed using the plasma gun previously described by our group. Antitumor activity was evaluated on HCT116, Mia Paca and H460 cancer cells which are representative models of colorectal carcinoma, pancreatic ductal adenocarcinoma and lung tumors respectively. These cells lines are potential future target for in situ plasma application. In vitro effects of plasma treatment on proliferation and viability were assessed by bioluminescence imaging (BLI). Figure 1: Effect of plasma gun treatment on tumor growth in vivoPlasma treatment induced a significant antitumor effect the different cells lines. The most sensitive cell line to plasma treatment was Mia Paca cells with a LD50 of 12s, then HCT-116 (LD50 18s) and H460 (LD50 28s) (figure 1). In HCT-116, plasma induces a decrease of cell proliferation and a decrease of cell mobility. This decrease of cell proliferation was the consequence of a massive cell cycle arrest in G2/M after plasma treatment. Moreover, an increase of apoptosis was observed in the treated cells. These results obtained with the plasma gun were closed to previous results obtained with our DBD and to other research group. Recent studies suggest the major importance of p53 in response to ROS generated by plasma treatment which is implicated in the cell cycle control. Our results on various cell lines including intracellular mutations like p53 or PTEN could explain the difference of cell sensitivity. Indeed, the most resistant cell line (H460) has various mutations including p53, KRAS and PIK3 while a Mia PACA cell has KRAS and p53 mutations. Implications of theses mutations in plasma cell sensitivity need to be further investigated. Non thermal plasma applied with plasma appears to be very promising and experiments are ongoing to evaluate antitumor activity of this strategy on representative cancer models in vivo