Plasma-activated medium inhibits cancer stem cell-like properties and exhibits a synergistic effect in combination with cisplatin in ovarian cancer.

Abstract

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. Here, we show that ovarian CSCs resistant to high-dose conventional chemotherapeutic agents used for ovarian cancer treatment exhibited dose-dependent sensitivity to PAM. In addition, PAM treatment reduced the expression of stem cell markers and sphere formation, along with the aldehyde dehydrogenase- or CD133-positive cell population. We further investigated the effect of PAM in combination with other chemotherapeutics on ovarian CSCs in vitro. 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. Taken together, our results indicate that PAM inhibits ovarian CSC traits and exhibits synergetic cytotoxicity with CDDP, demonstrating PAM as a promising intraparietal chemotherapy for enhancing antitumor efficacy and reducing side effects.

• Authors: Young Joo Lee, Sung Wook Kim, Min Hyung Jung, Young Sun Kim, Kyung Sook Kim, Dong Soo Suh, Ki Hyung Kim, Eun Ha Choi, Jongmin Kim, Byung Su Kwon
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 182 Pg. 276-288 (03 2022) ISSN: 1873-4596 [Electronic] United States
• PMID: 35276382 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Cisplatin

Topics

• Antineoplastic Agents (therapeutic use)
• Cell Line, Tumor
• Cell Proliferation
• Cisplatin (pharmacology, therapeutic use)
• Drug Resistance, Neoplasm
• Humans
• Neoplasm Recurrence, Local (drug therapy, metabolism)
• Neoplastic Stem Cells (metabolism)
• Ovarian Neoplasms (pathology)