Abstract
Pancreatic tumors are the gastrointestinal cancer with the worst prognosis in humans and with a survival rate of 5% at 5 years. Nowadays, no chemotherapy has demonstrated efficacy in terms of survival for this cancer. Previous study focused on the development of a new therapy by non thermal plasma showed significant effects on tumor growth for colorectal carcinoma and glioblastoma. To allow targeted treatment, a fibered plasma (Plasma Gun) was developed and its evaluation was performed on an orthotopic mouse model of human pancreatic carcinoma using a MIA PaCa2-luc bioluminescent cell line. The aim of this study was to characterize this pancreatic carcinoma model and to determine the effects of Plasma Gun alone or in combination with gemcitabine. During a 36 days period, quantitative BLI could be used to follow the tumor progression and we demonstrated that plasma gun induced an inhibition of MIA PaCa2-luc cells proliferation in vitro and in vivo and that this effect could be improved by association with gemcitabine possibly thanks to its radiosensitizing properties.
Highlights
Developments in plasma physics make possible to use Non Thermal Plasma (NTP) in cancer research
Considering the interesting antiproliferative potential of NTP and gemcitabine on MIA PaCa2-luc cells, the antitumor evaluation of these treatments was done in vivo on orthotopic xenografts
When comparing NTP+GEM and NTP groups, a significant difference of tumor weights, 12 mg and 42 mg respectively, was observed at D36 (p = 0,03). This observation shows that the plasma gun antitumor effects are increased by 33% when it is associated with gemcitabine. This experimental work reports that plasma gun, alone and more especially in combination with gemcitabine, induces a significant reduction of tumor growth in a mouse orthotopic model of human pancreatic cancer
Summary
Developments in plasma physics make possible to use Non Thermal Plasma (NTP) in cancer research. Photodynamic therapy uses light emission at a specific wavelength combined with a photosensitizing agent in order to generate Reactive Oxygen Species (ROS) in the treated area For this purpose, specific agents are needed to target the tumor and to avoid systemic side effects such as those associated to sun exposure of the patient. In a previous study, an increase in mice survival was observed with NTP on U87 human malignant glioma and melanoma heterotopic xenografts [3,4,5] This antitumor effect was demonstrated to be associated to ROS generation in the vicinity of the cells, leading to DNA damages, cells cycle arrest and apoptosis induction with limited side effects to healthy tissues [4,6]
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