{"title":"Intraperitoneal Treatment With Plasma-Activated Liquid Inhibits Peritoneal Metastasis In Ovarian Cancer Mouse Model","authors":"Kae Nakamura , Hiroaki Kajiyama , Yang Peng , Fumi Utsumi , Nobuhisa Yoshikawa , Hiromasa Tanaka , Masaaki Mizuno , Shinya Toyokuni , Masaru Hori , Fumitaka Kikkawa","doi":"10.1016/j.cpme.2017.12.073","DOIUrl":null,"url":null,"abstract":"<div><p><span>Non-thermal plasma in the medical field is a novel approach having various beneficial applications, such as sterilization, blood coagulation<span><span><span><span>, tissue regeneration and cancer </span>treatment. Recently, plasma-activated medium (PAM) has been widely studied in various types of cancer such as brain, lung, breast, gastric and ovarian cancer, due to its antitumor effect by inducing </span>apoptosis and DNA damage. [1] We previously demonstrated that PAM showed selective cytotoxicity towards </span>cancer cells, whereas normal cells remained unaffected. Moreover, PAM was shown to exert antitumor effects in acquired/natively chemo-resistant ovarian cancer cells. </span></span><em>In vivo</em><span><span> study, we also demonstrated the antitumor effects of PAM in a subcutaneous tumor formation xenograft<span> mouse model. [2] In the clinic, peritoneal metastasis is quite an issue for ovarian cancer patients and it is also a big obstacle for treatment. However, this model may not reflect the pathological conditions of ovarian cancer, with numerous micrometastatic disseminations in the </span></span>peritoneal cavity.</span></p><p><span>In this study, we selected between the two ovarian cancer cell lines ES2 and SKOV3, which could stably show tumor formation </span><em>in vivo</em>, and decided to use ES2 for the following <em>in vivo</em><span><span> experiments because ES2 was more sensitive than SKOV3 to the effects of PAM. We examined whether PAM therapy affects survival in a mouse model of intraperitoneal injection. Six-week-old female BALB/c nude mice were intraperitoneally injected with ES2 cells and then the mice were treated with PAM or non-plasma-irradiated medium as a control once a day for a total of 3 days. As shown in the figure, Survival analysis was performed using the Kaplan–Meier method, indicating that the survival rates were poorer in the control group than in the PAM therapy group (P < 0.01). However, body weight was not significantly different between the two groups. We also assessed intraperitoneal dissemination in a mouse model by the </span>bioluminescence<span> value from luciferase-expressing ES2 cells, the peritoneal cancer metastasis state was monitored using the IVIS 200 Imaging System. Intraperitoneal PAM injection therapy markedly inhibited intraperitoneal metastasis of ES2 cells. [3]</span></span><span><figure><span><img><ol><li><span>Download : <span>Download high-res image (81KB)</span></span></li><li><span>Download : <span>Download full-size image</span></span></li></ol></span></figure></span></p><p>Overall survival</p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.073","citationCount":"7","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Plasma Medicine","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2212816617300987","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 7
Abstract
Non-thermal plasma in the medical field is a novel approach having various beneficial applications, such as sterilization, blood coagulation, tissue regeneration and cancer treatment. Recently, plasma-activated medium (PAM) has been widely studied in various types of cancer such as brain, lung, breast, gastric and ovarian cancer, due to its antitumor effect by inducing apoptosis and DNA damage. [1] We previously demonstrated that PAM showed selective cytotoxicity towards cancer cells, whereas normal cells remained unaffected. Moreover, PAM was shown to exert antitumor effects in acquired/natively chemo-resistant ovarian cancer cells. In vivo study, we also demonstrated the antitumor effects of PAM in a subcutaneous tumor formation xenograft mouse model. [2] In the clinic, peritoneal metastasis is quite an issue for ovarian cancer patients and it is also a big obstacle for treatment. However, this model may not reflect the pathological conditions of ovarian cancer, with numerous micrometastatic disseminations in the peritoneal cavity.
In this study, we selected between the two ovarian cancer cell lines ES2 and SKOV3, which could stably show tumor formation in vivo, and decided to use ES2 for the following in vivo experiments because ES2 was more sensitive than SKOV3 to the effects of PAM. We examined whether PAM therapy affects survival in a mouse model of intraperitoneal injection. Six-week-old female BALB/c nude mice were intraperitoneally injected with ES2 cells and then the mice were treated with PAM or non-plasma-irradiated medium as a control once a day for a total of 3 days. As shown in the figure, Survival analysis was performed using the Kaplan–Meier method, indicating that the survival rates were poorer in the control group than in the PAM therapy group (P < 0.01). However, body weight was not significantly different between the two groups. We also assessed intraperitoneal dissemination in a mouse model by the bioluminescence value from luciferase-expressing ES2 cells, the peritoneal cancer metastasis state was monitored using the IVIS 200 Imaging System. Intraperitoneal PAM injection therapy markedly inhibited intraperitoneal metastasis of ES2 cells. [3]
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