Effectiveness of plasma treatment on pancreatic cancer cells

Abstract

Non-equilibrium atmospheric pressure plasma (NEAPP) has attracted attention in cancer therapy. We explored the indirect effect of NEAPP through plasma-activated medium (PAM) on pancreatic cancer cells in vitro and in vivo. In this study, four pancreatic cancer cell lines were used and the antitumor effects of PAM treatment were evaluated using a cell proliferation assay. To explore functional mechanisms, morphological change and caspase-3/7 activation in cells were also assessed. Furthermore, reactive oxygen species (ROS) generation in cells was examined and N-acetyl cysteine (NAC), an intracellular ROS scavenger, was tested. Finally, the antitumor effect of local injection of PAM was investigated in a mouse xenograft model. We found that PAM treatment had lethal effect on pancreatic cancer cells. Typical morphological findings suggestive of apoptosis such as vacuolization of cell membranes, small and round cells and aggregation of cell nuclei, were observed in the PAM treated cells. Caspase-3/7 activation was detected in accordance with the observed morphological changes. Additionally, ROS uptake was observed in all cell lines tested, while the antitumor effects of PAM were completely inhibited with NAC. In the mouse xenograft model, the calculated tumor volume on day 28 in the PAM treatment group was significantly smaller compared with the control group [28±22 vs. 89±38 (mm3 ± SD), p=0.0031]. These results show that PAM treatment of pancreatic cancer might be a promising therapeutic strategy.

State of the art in medical applications using non-thermal atmospheric pressure plasma

“…75, (Hattori et al 2015)] and pretreatment with N-acetyl cysteine (NAC), a ROS scavenger, prevented the anti-tumor effect of PAM (Fig. 76).…”

“…Intraperitoneal (IP) treatment with PAM is a promising option for cancers such as ovarian (Utsumi et al 2013, gastric (Torii et al 2014) and pancreatic (Hattori et al 2015) that have disseminated throughout the peritoneal cavity . It is difficult to remove intraperitoneally disseminated cancers by surgery or radiation.…”

“…72, (Tanaka et al 2014b)]. (Hattori et al 2015). After PAM treatment, ROS uptake in pancreatic cancer cells (PANC-1) was observed using fluorescence microscopy.…”

“…Scale bars represent 50 lm Fig. 76 Pretreatment with NAC prevented the anti-tumor effect of PAM on pancreatic cancer cells (Hattori et al 2015). Pancreatic cancer cells (PANC-1) were seeded at a density of 1 9 10 3 , 5 9 10 3 , and 1 9 10 4 cells/well in a 96-well plate.…”

Plasma Treatment of Ovarian Cancer Cells Mitigates Their Immuno-Modulatory Products Active on THP-1 Monocytes

“…Over the last two decades, potential applications have extended from eradicating microorganisms during wound healing to inactivating tumor cells [2]. Today, effective killing of the latter has been demonstrated for different types of cancers including head and neck [3][4][5], leukemia [6][7][8], glioblastoma [9][10][11], pancreas [12][13][14], malignant melanoma [15][16][17], colon [18][19][20], prostate [21][22][23], osteosarcoma [24][25][26], and ovarian [27][28][29]. It has been established the ROS/RNS are the main drivers of antitumor plasma effects [30][31][32].…”