Plasma-Activated Medium Inhibites Metastatic Activities Of Ovarian Cancer Cells In Vitro Via Repressing Mapk Pathway

Abstract

Ovarian cancer is among the most malignant gynecologic cancers since peritoneal dissemination often occurs at the diagnosis of these patients. The 5-year survival rate is less than 50%. Recently, non-equilibrium atmospheric pressure plasma (NEAPP) has been introduced in medical field. We have already demonstrated the cytotoxic effect of the direct plasma exposure to ovarian cancer cells. However, it is difficult to expose cancer cells to plasma gas intraperitoneally. Thus, we established the system of plasma-activated medium (PAM) to treat ovarian cancer indirectly instead of a direct exposure to plasma [1].

In our previous works, it was demonstrated that PAM significantly inhibited proliferation ability of ovarian cancer cells, with fibroblast cells remaining unaffected though. Both in vitro and in vivo study had confirmed the cytotoxic effect of PAM to ovarian cancer. However, it still remains unknown whether PAM can affect metastasis of ovarian cancer cells, which is the fatal problem of ovarian cancer patients [2].

In this study, we tried to investigate PAM’s anti-metastasis effect in vitro and the underneath mechanism. Firstly, we performed wound-healing and transwell assay on ES2, one of ovarian cancer cell lines. We found that the cell migration and invasion abilities were significantly inhibited by PAM. Secondly, we established a co-culture system by seeding ES2 cells onto monolayer of peritoneal mesothelial cells, which models the initial step of ovarian cancer cells metastasis in human peritoneal cavity, and it was found that PAM significantly repressed ES2 cells to implant onto mesothelial cells. Moreover, mechanism study showed both mRNA and protein levels of MMP-9 were inhibited by PAM. And PAM significantly inhibited the phosphorylation of JNK1/2 MAPK and p38 MAPK (figure 1), which indicated that inhibition of MMP-9 was dependent on MAPK pathway [3].

In summary, it is indicated in this work that PAM presents efficient inhibitory effect towards ovarian cancer cells metastasis in vitro. Moreover, PAM’s anti-metastasis effect is implemented by repressing the activation MAPK pathway, resulting in de-activation of downstream target MMP-9, thus leading to suppression of cell migration and invasion. In the near future, it might be a new clinical strategy for metastatic ovarian cancer patients to choose PAM therapy via intaperitoneal treatment.

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Fig. 1