Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya, 466-8550, Japan.
Institute of Innovation for Future Society, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8603, Japan.
Sci Rep. 2017 Jul 20;7(1):6085. doi: 10.1038/s41598-017-05620-6.
Non-thermal atmospheric pressure plasma has been proposed as a new therapeutic tool for cancer treatment. Recently, plasma-activated medium (PAM) has been widely studied in various cancer types. However, there are only few reports demonstrating the anti-tumour effects of PAM in an animal model reflecting pathological conditions and the accompanying mechanism. Here we investigated the inhibitory effect of PAM on the metastasis of ovarian cancer ES2 cells in vitro and in vivo. We demonstrated that ES2 cell migration, invasion and adhesion were suppressed by PAM at a certain PAM dilution ratio, whereas cell viability remained unaffected. In an in vivo mouse model of intraperitoneal metastasis, PAM inhibited peritoneal dissemination of ES2 cells, resulting in prolonged survival. Moreover, we assessed the molecular mechanism and found that MMP-9 was decreased by PAM. On further investigation, we also found that PAM prevented the activation of the MAPK pathway by inhibiting the phosphorylation of JNK1/2 and p38 MAPK. These findings indicate that PAM inhibits the metastasis of ovarian cancer cells through reduction of MMP-9 secretion, which is critical for cancer cell motility. Our findings suggest that PAM intraperitoneal therapy may be a promising treatment option for ovarian cancer.
非热常压等离子体已被提议作为癌症治疗的一种新的治疗工具。最近，等离子体激活介质（PAM）在各种癌症类型中得到了广泛研究。然而，仅有少数报道表明 PAM 在反映病理条件和伴随机制的动物模型中具有抗肿瘤作用。在这里，我们研究了 PAM 在体外和体内对卵巢癌细胞 ES2 转移的抑制作用。我们证明，在一定的 PAM 稀释比下，PAM 抑制 ES2 细胞的迁移、侵袭和黏附，而细胞活力不受影响。在腹腔转移的小鼠模型中，PAM 抑制 ES2 细胞的腹膜扩散，导致生存时间延长。此外，我们评估了分子机制，发现 PAM 降低了 MMP-9。进一步研究还发现，PAM 通过抑制 JNK1/2 和 p38 MAPK 的磷酸化来阻止 MAPK 通路的激活。这些发现表明，PAM 通过减少 MMP-9 的分泌来抑制卵巢癌细胞的转移，这对于癌细胞的运动至关重要。我们的研究结果表明，PAM 腹腔内治疗可能是治疗卵巢癌的一种有前途的治疗选择。
