Cold atmospheric plasma-activated liquid inhibits peritoneal metastasis in drug-resistant ovarian cancer by targeting the epithelial-mesenchymal transition.

IF 3.2 3区 医学 Q2 ONCOLOGY
Jinren Liu, Xiangni Wang, Yixin Cui, Jiajia Lu, Zhirou He, Yulin Xu, Rongrong Li, Guimin Xu, Lingge Gao, Xiaolin Fan, Xili Wu, Xingmin Shi, Guanjun Zhang
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Abstract

Ovarian cancer remains a significant challenge in oncology due to its aggressive nature, late-stage diagnosis, and high rates of chemoresistance, particularly to platinum-based therapies like cisplatin. The epithelial-mesenchymal transition (EMT) is a key driver of ovarian cancer metastasis and drug resistance, highlighting the need for novel therapeutic strategies. Cold atmospheric plasma (CAP) and plasma-activated liquids (PAL), including plasma-activated medium (PAM) and saline (PAS), have emerged as promising anticancer agents, generating reactive oxygen and nitrogen species (RONS) that selectively target cancer cells. This study investigates the potential of PAL to inhibit the invasion and metastasis of cisplatin-resistant ovarian cancer cells and explores its synergistic effects with cisplatin. In vitro, PAM reduced proliferation, migration, and invasion of cisplatin-resistant ovarian cancer cells (A2780/DDP and SKOV3/DDP) while downregulating EMT-related proteins (N-cadherin, β-catenin, vimentin). H2O2 in PAM inhibit the PI3K/AKT/GSK3β pathway, promoting degradation of EMT regulators Snail, Slug, and β-catenin. Combining PAM with cisplatin enhanced therapeutic efficacy, reducing cell viability and metastatic potential. In vivo studies using an orthotopic mouse model further confirmed that PAS combined with low-dose cisplatin effectively suppressed tumor growth and metastasis with minimal side effects. These findings underscore the potential of PAL as an adjuvant therapy for cisplatin-resistant ovarian cancer, offering a novel approach to overcome drug resistance and inhibit metastasis. Future research should focus on optimizing treatment protocols and elucidating the molecular mechanisms underlying the synergistic effects of PAL and cisplatin.

低温大气血浆活化液通过靶向上皮-间质转化抑制耐药卵巢癌腹膜转移。
由于卵巢癌的侵袭性、晚期诊断和高耐药率,特别是对顺铂等铂基治疗,卵巢癌仍然是肿瘤学中的一个重大挑战。上皮-间质转化(epithelial-mesenchymal transition, EMT)是卵巢癌转移和耐药的关键驱动因素,因此需要新的治疗策略。低温大气等离子体(CAP)和等离子体活化液(PAL),包括等离子体活化介质(PAM)和生理盐水(PAS),已成为有前途的抗癌药物,产生选择性靶向癌细胞的活性氧和活性氮(RONS)。本研究探讨PAL抑制顺铂耐药卵巢癌细胞侵袭转移的潜力,并探讨其与顺铂的协同作用。在体外,PAM可降低顺铂耐药卵巢癌细胞(A2780/DDP和SKOV3/DDP)的增殖、迁移和侵袭,同时下调emt相关蛋白(N-cadherin、β-catenin、vimentin)。PAM中的H2O2抑制PI3K/AKT/GSK3β通路,促进EMT调节因子Snail, Slug和β-catenin的降解。PAM联合顺铂可提高治疗效果,降低细胞活力和转移潜能。原位小鼠模型的体内研究进一步证实,PAS联合低剂量顺铂有效抑制肿瘤生长和转移,副作用最小。这些发现强调了PAL作为顺铂耐药卵巢癌辅助治疗的潜力,提供了一种克服耐药和抑制转移的新方法。未来的研究应侧重于优化治疗方案和阐明PAL和顺铂协同作用的分子机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.80
自引率
5.00%
发文量
55
审稿时长
12 months
期刊介绍: The Journal''s scope encompasses all aspects of metastasis research, whether laboratory-based, experimental or clinical and therapeutic. It covers such areas as molecular biology, pharmacology, tumor biology, and clinical cancer treatment (with all its subdivisions of surgery, chemotherapy and radio-therapy as well as pathology and epidemiology) insofar as these disciplines are concerned with the Journal''s core subject of metastasis formation, prevention and treatment.
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