Introduction Ovarian cancer stem-like cells (CSCs) have been implicated in tumor recurrence, metastasis, and drug resistance. Accumulating evidence has demonstrated the antitumor effect of plasma-activated medium (PAM) in various carcinomas, including ovarian cancer. Thus, PAM represents a novel onco-therapeutic strategy. However, its impact on ovarian CSCs is unclear.

Methods In this study, we assessed whether PAM regulates the stemness properties in a CSC-like spheroid model. Furthermore, we investigated the potential enhanced anti-cancer effects of combination treatment with conventional chemotherapeutic agents and PAM using in vitro and in vivo models.

Results PAM exhibited synergistic cytotoxicity with cisplatin (CDDP) but not with paclitaxel and doxorubicin. In a peritoneal metastasis xenograft model established via intraperitoneal spheroid injection, PAM intraperitoneal therapy significantly suppressed peritoneal carcinomatosis (tumor size and number), with a more significant decrease observed due to the combined effects of PAM and CDDP with no side effects.

Conclusion/Implications We demonstrated the anti-CSC activity of PAM and the synergistic cytotoxic effect of the PAM and CDDP combination therapy on ovarian CSCs. Analysis of intraperitoneal PAM and CDDP combination therapy in a spheroid culture xenograft model of ovarian cancer showed promising results. Further studies are needed to determine the molecular mechanism underlying the synergistic anti-cancer effects of PAM and anti-cancer drugs to enhance their antitumor efficacy against ovarian CSCs and reduce the relevant side effects.