Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Ishikawa 920-0293, Japan.
Department of Pediatrics, Wuhan Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
Oxid Med Cell Longev. 2020 Dec 28;2020:8262730. doi: 10.1155/2020/8262730. eCollection 2020.
Peroxiredoxin 4 (PRDX4), initially reported as an antioxidant, is overexpressed in lung cancer and participates in its progression. However, its role in the urethane-induced lung tumor model is undetermined. The aim of this study was to investigate the effect of PRDX4 overexpression on carcinogen-induced lung tumor development. Human PRDX4 overexpression transgenic (Tg) mice ( ) and non-Tg mice were intraperitoneally injected with urethane to induce lung tumor. After 6 months, tumor formation was compared between groups and possible mechanisms for the difference in tumor development were investigated. The serum and lung PRDX4 expressions were enhanced after urethane stimulation in Tg mice. Both the average number of tumors (≥0.5 mm) and tumor diameter per mouse in the Tg group were significantly larger than in non-Tg controls, while body weight was lower in the Tg group. Compared with non-Tg controls, tumor cell proliferation was enhanced, while tumor cell apoptosis was suppressed in Tg mice. Systemic oxidative stress and oxidative stress in lung tumors were inhibited by PRDX4 overexpression. The balance of prooxidant enzymes and antioxidant enzymes was also shifted to a decreased level in Tg tumor. In lung tumor tissue, the density of microvessel penetrated into tumor was higher in the Tg group; macrophage infiltration was enhanced in Tg tumors, while there was no difference in T lymphocyte infiltration; the expressions of cytokines, including interleukin-1 beta (IL-1) and matrix metallopeptidase 9 (MMP9), were elevated in Tg tumors, which resulted from enhanced phosphorylation of nuclear factor-B p65 (NF-B p65) and c-Jun, respectively. In conclusion, PRDX4 overexpression modulated tumor microenvironment and promoted tumor development in the mouse urethane-induced lung cancer model.
过氧化物酶 4（PRDX4）最初被报道为一种抗氧化剂，在肺癌中过度表达，并参与其进展。然而，其在尿烷诱导的肺癌肿瘤模型中的作用尚未确定。本研究旨在探讨 PRDX4 过表达对致癌物诱导的肺肿瘤发生的影响。人 PRDX4 过表达转基因（Tg）小鼠（）和非 Tg 小鼠经腹腔注射尿烷诱导肺肿瘤。6 个月后，比较两组肿瘤形成情况，并探讨肿瘤发展差异的可能机制。PRDX4 过表达的 Tg 小鼠在尿烷刺激后血清和肺组织中的 PRDX4 表达增强。Tg 组小鼠的平均肿瘤数（≥0.5mm）和每只小鼠的肿瘤直径均显著大于非 Tg 对照组，而 Tg 组的体重较低。与非 Tg 对照组相比，Tg 小鼠的肿瘤细胞增殖增强，而肿瘤细胞凋亡受到抑制。PRDX4 过表达抑制全身氧化应激和肺肿瘤中的氧化应激。促氧化剂酶和抗氧化酶的平衡也向 Tg 肿瘤中降低的水平转移。在肺肿瘤组织中，Tg 组肿瘤中渗透到肿瘤的微血管密度较高；Tg 肿瘤中巨噬细胞浸润增强，而 T 淋巴细胞浸润无差异；细胞因子（包括白细胞介素-1β（IL-1）和基质金属蛋白酶 9（MMP9））的表达在 Tg 肿瘤中升高，这分别是由于核因子-B p65（NF-B p65）和 c-Jun 的磷酸化增强所致。总之，PRDX4 过表达调节肿瘤微环境并促进小鼠尿烷诱导的肺癌模型中的肿瘤发展。
