Selective Killing of Ovarian Cancer Cells through Induction of Apoptosis by a Nonequilibrium Atmospheric Pressure Plasma
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Selective Killing of Ovarian Cancer Cells through Induction of Apoptosis by a Nonequilibrium Atmospheric Pressure Plasma Hiromasa Tanaka1, Sachiko Iseki1, Kae Nakamura2, Moemi Hayashi2, Hiroki Kondo1, Hiroaki Kajiyama2, Hiroyuki Kano3, Fumitaka Kikkawa2, Masaru Hori1 1
Department of Electrical Engineering and Computer Science, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan 2 Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya 466-8550, Japan 3 NU Eco-Engineering Co., Ltd., 1237-87 Umazutsumi, Kurozasa-cho, Miyoshi-shi, Nishikamogun, Aichi 470-0201, Japan ABSTRACT Two independent ovarian cancer cell lines and fibroblast controls were treated with nonequilibrium atmospheric pressure plasma (NEAPP). Most ovarian cancer cells were detached from the culture dish by continuous plasma treatment to a single spot on the dish. Next, the plasma source was applied over the whole dish using a robot arm. In vitro cell proliferation assays showed that plasma treatments significantly decreased proliferation rates of ovarian cancer cells compared to fibroblast cells. FACS and Western blot analysis showed that plasma treatment of ovarian cancer cells induced apoptosis. NEAPP could be a promising tool for therapy for ovarian cancers. INTRODUCTION Epithelial ovarian carcinoma is the leading cause of death from gynecologic malignancies, and the fifth most frequent cause of cancer death in women [1]. Most patients are diagnosed at the advanced stage of ovarian cancer since it frequently remains clinically silent until then. Although aggressive cytoreductive surgery and chemotherapy have been employed in an attempt to improve the survival rate in patients over the past three decades, the 5-year survival rate is still relatively low. The low survival rate is due to recurrence through peritoneal dissemination. This is the most common metastatic process of epithelial ovarian carcinoma and is found in over 75% of all cases. The response rate to chemotherapeutic compounds is only 15% to 30%, perhaps due to the rise of resistance to such drugs, and new treatments are needed for such tumors. Recently developed anti-cancer drugs [2, 3], including those that target ovarian cancer, rely on platinum compounds. This class of drugs kills rapidly dividing cancer cells; however, not only cancer cells, but also rapidly dividing normal cells are targeted. Selective killing of cancer cells is important for any anti-cancer therapy, and innovative cancer therapeutic strategies are still needed. Recently, medical applications using NEAPPs have attracted attention in the field of medicine because cells are not vacuum-compatible, and thermal damage to cells is negligible with appropriate tuning of the NEAPP parameters and experimental setup [4, 5]. It is not surprising that researchers in plasma medicine have studied the possible applications in cancer therapy, as some pioneering work has shown that NEAPP exerts anti-tumor effects on lung carc
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