过氧化还原蛋白 1 (PRDX1) 是一种降低 HepG2 人肝细胞癌细胞 (HCC) 细胞中活性氧和氮物种水平的关键酶，在氧化应激下调节 HCC 细胞干性中的作用及其潜在机制在很大程度上仍未被探索。在这里，我们研究了非热等离子体在 HCC 中靶向癌症干细胞 (CSC) 的治疗潜力，重点关注抗氧化应激的机制和 PRDX1 的作用。通过使用血浆激活培养基模拟氧化应激条件，我们发现PRDX1水平的降低导致HepG2细胞凋亡显着增加，这表明PRDX1在CSC的氧化应激防御机制中发挥关键作用。此外，我们发现HepG2细胞具有更高的球体形成能力和干细胞标志物（CD133、c-Myc和OCT-4）水平升高，表明其具有很强的干性。有趣的是，HepG2 细胞中 PRDX1 的表达明显高于其他 HCC 细胞类型（例如 Hep3B 和 Huh7 细胞），而其他 PRDX 家族蛋白（PRDX 2-6）的表达水平相对一致。 Conoidin A 抑制 PRDX1 表达和过氧化物酶活性导致干细胞性状显着降低并增加细胞死亡率。此外，在异种移植小鼠模型中，等离子激活介质（PAM）治疗后，PRDX1 下调显着抑制实体瘤的形成。这些发现强调了 PRDX 1 在氧化应激下调节 HCC 细胞干性和凋亡中的关键作用，强调 PRDX1 作为基于 NTP 的 HCC 治疗的一个有前途的治疗靶点。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

The role of peroxiredoxin 1 (PRDX1), a crucial enzyme that reduces reactive oxygen and nitrogen species levels in HepG2 human hepatocellular carcinoma (HCC) cells, in the regulation of HCC cell stemness under oxidative stress and the underlying mechanisms remain largely unexplored. Here, we investigated the therapeutic potential of non-thermal plasma in targeting cancer stem cells (CSCs) in HCC, focusing on the mechanisms of resistance to oxidative stress and the role of PRDX1. By simulating oxidative stress conditions using the plasma-activated medium, we found that a reduction in PRDX1 levels resulted in a considerable increase in HepG2 cell apoptosis, suggesting that PRDX1 plays a key role in oxidative stress defense mechanisms in CSCs. Furthermore, we found that HepG2 cells had higher spheroid formation capability and increased levels of stem cell markers (CD133, c-Myc, and OCT-4), indicating strong stemness. Interestingly, PRDX1 expression was notably higher in HepG2 cells than in other HCC cell types such as Hep3B and Huh7 cells, whereas the expression levels of other PRDX family proteins (PRDX 2-6) were relatively consistent. The inhibition of PRDX1 expression and peroxidase activity by conoidin A resulted in markedly reduced stemness traits and increased cell death rate. Furthermore, in a xenograft mouse model, PRDX1 downregulation considerably inhibited the formation of solid tumors after plasma-activated medium (PAM) treatment. These findings underscore the critical role of PRDX 1 in regulating stemness and apoptosis in HCC cells under oxidative stress, highlighting PRDX1 as a promising therapeutic target for NTP-based treatment in HCC.Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.