Department of Biology, Fairfield University, Fairfield, Connecticut, USA.
Redox Rep. 2009;14(6):275-84. doi: 10.1179/135100009X12525712409652.
Peroxiredoxins are thiol-specific antioxidants that catalyze the reduction of cellular peroxides and protect cells from ROS-mediated damage and death. Peroxiredoxin gene expression is up-regulated in a number of cancers, suggesting a possible role in cancer cell maintenance. Prdx6, a cytoplasmic protein elevated in certain cancers, is highly expressed in liver and transcriptionally regulated by various oxidative stresses. In the present study, we found that the cancerous Hepa1-6 hepatoma cell line is significantly more resistant to peroxide-induced cytotoxicity than the non-cancerous H2.35 cell line. We also demonstrated that Hepa1-6 cells express approximately 3-fold more Prdx6 mRNA and 2.5-fold more Prdx6 protein than H2.35 cells. Treatment with mithramycin A resulted in a nearly 20% reduction in Prdx6 mRNA in Hepa1-6 cells, suggesting a possible role for Sp1 in Prdx6 up-regulation. We hypothesized that suppression of Prdx6 in Hepa1-6 cells would increase susceptibility to peroxide-induced cell death. Transient transfection of Hepa1-6 cells with Prdx6 siRNA led to a marked reduction in Prdx6 expression, and an increase in peroxide-induced cytotoxicity by apoptosis. Together, these data demonstrate an important anti-apoptotic function for Prdx6 in cancerous liver cells, and suggest that its up-regulation may be a tumor-supportive adaptation in cancerous states.
过氧化物酶是硫醇特异性抗氧化剂，可催化细胞过氧化物的还原，保护细胞免受 ROS 介导的损伤和死亡。过氧化物酶基因在许多癌症中表达上调，表明其在维持癌细胞中可能发挥作用。细胞质蛋白 Prdx6 在某些癌症中升高，在肝脏中高度表达，并受多种氧化应激转录调节。在本研究中，我们发现肝癌 Hepa1-6 细胞系对过氧化氢诱导的细胞毒性的抵抗力明显高于非癌细胞系 H2.35。我们还证明，Hepa1-6 细胞表达的 Prdx6 mRNA 约是 H2.35 细胞的 3 倍，Prdx6 蛋白是 H2.35 细胞的 2.5 倍。米托蒽醌 A 处理可使 Hepa1-6 细胞中的 Prdx6 mRNA 减少近 20%，提示 Sp1 可能在 Prdx6 上调中起作用。我们假设 Hepa1-6 细胞中 Prdx6 的抑制会增加对过氧化氢诱导的细胞死亡的敏感性。用 Prdx6 siRNA 瞬时转染 Hepa1-6 细胞可显著降低 Prdx6 表达，并增加过氧化氢诱导的细胞毒性通过细胞凋亡。总之，这些数据表明 Prdx6 在肝癌细胞中具有重要的抗凋亡功能，并提示其上调可能是癌症状态下肿瘤支持的适应性。
