Lee Young Joo, Kim Sung Wook, Jung Min Hyung, Kim Young Sun, Kim Kyung Sook, Suh Dong Soo, Kim Ki Hyung, Choi Eun Ha, Kim Jongmin, Kwon Byung Su
Department of Obstetrics and Gynecology, School of Medicine, Kyung Hee Medical Center, Kyung Hee University, Seoul, 02447, South Korea.
Department of Biomedical Engineering, College of Medicine, Kyung Hee University, Seoul, 02447, South Korea.
Free Radic Biol Med. 2022 Mar;182:276-288. doi: 10.1016/j.freeradbiomed.2022.03.001. Epub 2022 Mar 9.
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.
卵巢癌干细胞（CSCs）与肿瘤复发、转移及耐药性有关。越来越多的证据表明，血浆激活培养基（PAM）在包括卵巢癌在内的各种癌症中具有抗肿瘤作用。因此，PAM代表了一种新的肿瘤治疗策略。然而，其对卵巢癌干细胞的影响尚不清楚。在此，我们表明，对用于卵巢癌治疗的高剂量传统化疗药物耐药的卵巢癌干细胞对PAM表现出剂量依赖性敏感性。此外，PAM处理降低了干细胞标志物的表达和球体形成，以及醛脱氢酶或CD133阳性细胞群体。我们进一步研究了PAM与其他化疗药物联合对体外卵巢癌干细胞的影响。PAM与顺铂（CDDP）表现出协同细胞毒性，但与紫杉醇和阿霉素无协同作用。在通过腹腔注射球体建立的腹膜转移异种移植模型中，PAM腹腔治疗显著抑制了腹膜癌（肿瘤大小和数量），由于PAM和CDDP的联合作用，观察到更显著的减少，且无副作用。综上所述，我们的结果表明，PAM抑制卵巢癌干细胞特性，并与CDDP表现出协同细胞毒性，证明PAM是一种有前景的腹腔内化疗药物，可提高抗肿瘤疗效并减少副作用。
