title: Effect of indirect nonequilibrium atmospheric pressure plasma on anti-proliferative activity against chronic chemo-resistant ovarian cancer cells in vitro and in vivo.
abstract: OBJECTIVE
  Nonequilibrium atmospheric pressure plasma (NEAPP) therapy has recently been focused on as a novel medical practice. Using cells with acquired paclitaxel/cisplatin resistance, we elucidated effects of indirect NEAPP-activated medium (NEAPP-AM) exposure on cell viability and tumor growth in vitro and in vivo.
  
  
  METHODS
  Using chronic paclitaxel/cisplatin-resistant ovarian cancer cells, we applied indirect NEAPP-exposed medium to cells and xenografted tumors in a mouse model. Furthermore, we examined the role of reactive oxygen species (ROS) or their scavengers in the above-mentioned EOC cells.
  
  
  RESULTS
  We assessed the viability of NOS2 and NOS3 cells exposed to NEAPP-AM, which was prepared beforehand by irradiation with NEAPP for the indicated time. In NOS2 cells, viability decreased by approximately 30% after NEAPP-AM 120-sec treatment (P<0.01). The growth-inhibitory effects of NEAPP-AM were completely inhibited by N-acetyl cysteine treatment, while L-buthionine-[S, R]-sulfoximine, an inhibitor of the ROS scavenger used with NEAPP-AM, decreased cell viability by 85% after NEAPP-AM 60-sec treatment(P<0.05) and by 52% after 120 sec, compared to the control (P<0.01). In the murine subcutaneous tumor-formation model, NEAPP-AM injection resulted in an average inhibition of the NOS2 cell-inoculated tumor by 66% (P<0.05) and NOS2TR cell-inoculated tumor by 52% (P<0.05), as compared with the control.
  
  
  CONCLUSIONS
  We demonstrated that plasma-activated medium also had an anti-tumor effect on chemo-resistant cells in vitro and in vivo. Indirect plasma therapy is a promising treatment option for EOC and may contribute to a better patient prognosis in the future.
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
authors.forename: Fumi
authors.initials: F
authors.lastname: Utsumi
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kajiyama
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
authors.forename: Kae
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Electrical Engineering and Computer Science, Graduate School of Engineering, Nagoya University, Chikusa-ku, Nagoya, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Center for Advanced Medicine and Clinical Research, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Mizuno
authors.affiliation: Department of Electrical Engineering and Computer Science, Graduate School of Engineering, Nagoya University, Chikusa-ku, Nagoya, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Ishikawa
authors.affiliation: Department of Electrical Engineering and Computer Science, Graduate School of Engineering, Nagoya University, Chikusa-ku, Nagoya, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kondo
authors.affiliation: NU Eco-Engineering Co., Ltd., Miyoshi-shi, Aichi, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kano
authors.affiliation: Department of Electrical Engineering and Computer Science, Graduate School of Engineering, Nagoya University, Chikusa-ku, Nagoya, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Hori
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Kikkawa
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001274:Atmospheric Pressure; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel; D058626:Plasma Gases / Q000627:therapeutic use*; D043823:Taxoids / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D058626:Plasma Gases; D043823:Taxoids; D017239:Paclitaxel; D002945:Cisplatin