Stem Cell and Regenerative Biology Laboratory, College of Life Science & Biotechnology, Heilongjiang Bayi Agricultural University, Heilongjiang, Daqing, 163319, China.
Stem Cell and Regenerative Biology Laboratory, College of Life Science & Biotechnology, Heilongjiang Bayi Agricultural University, Heilongjiang, Daqing, 163319, China; Plasma Bioscience Research Center, Department of Electrical and Biological Physics, Kwangwoon University, Seoul, 01897, Republic of Korea.
Biochem Biophys Res Commun. 2024 Dec 17;738:150522. doi: 10.1016/j.bbrc.2024.150522. Epub 2024 Aug 8.
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.
过氧化物还原酶 1（PRDX1）是一种重要的酶，可降低 HepG2 人肝癌（HCC）细胞中活性氧和氮物种的水平，但其在氧化应激下调节 HCC 细胞干性的作用及其潜在机制在很大程度上仍未得到探索。在这里，我们研究了非热等离子体在针对 HCC 中的癌症干细胞（CSC）的治疗潜力，重点研究了对氧化应激的抵抗机制以及 PRDX1 的作用。通过使用等离子体激活的介质模拟氧化应激条件，我们发现 PRDX1 水平的降低导致 HepG2 细胞凋亡显著增加，表明 PRDX1 在 CSCs 的氧化应激防御机制中起关键作用。此外，我们发现 HepG2 细胞具有更高的球体形成能力和更高水平的干细胞标记物（CD133、c-Myc 和 OCT-4），表明其具有较强的干性。有趣的是，PRDX1 在 HepG2 细胞中的表达明显高于其他 HCC 细胞类型（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。用 conoidin A 抑制 PRDX1 的表达和过氧化物酶活性导致干性特征明显减少和细胞死亡率增加。此外，在异种移植小鼠模型中，PRDX1 下调在等离子体激活的介质（PAM）治疗后大大抑制了实体瘤的形成。这些发现强调了 PRDX1 在调节氧化应激下 HCC 细胞干性和细胞凋亡中的关键作用，突出了 PRDX1 作为基于 NTP 治疗 HCC 的有前途的治疗靶点。
