Kahlos K, Soini Y, Säily M, Koistinen P, Kakko S, Pääkkö P, Holmgren A, Kinnula V L
Department of Internal Medicine, University of Oulu, Kajaanintie 50, FIN-90220, Oulu, Finland.
Int J Cancer. 2001 May 20;95(3):198-204. doi: 10.1002/1097-0215(20010520)95:3<198::aid-ijc1034>3.0.co;2-f.
Thioredoxin (Trx) with a redoxactive dithiol together with NADPH and thioredoxin reductase (TrxR) is a major disulfide reductase regulating cellular redox state and cell proliferation and possibly contributing to the drug resistance of malignant cells. We assessed the Trx system in malignant pleural mesothelioma cell lines, in nonmalignant pleural mesothelium and in biopsies of malignant pleural mesothelioma. The mRNA and immunoreactive proteins of Trx and cytosolic and mitochondrial TrxR were positive in all four human mesothelioma cell lines investigated. Six cases of nonmalignant, histologically healthy pleural mesothelium showed no Trx or TrxR immunoreactivity, whereas immunohistochemistry on 26 biopsies of human malignant pleural mesothelioma showed positive Trx in all cases and positive TrxR in 23 (88%) of the cases. Moderate or strong immunoreactivity for Trx or TrxR was detected in 85% (22 cases) and 61% (14 cases) of the mesothelioma cases, respectively. Both Trx and TrxR staining patterns were mainly diffuse and cytoplasmic, but in 39% of the mesothelioma cases prominent nuclear staining could also be detected. Although staining for Trx and TrxR was seen in tumor cells, no significant association could be demonstrated between Trx or TrxR expression and tumor cell proliferation or apoptosis in the biopsies of mesothelioma. There was no significant association between the intensity of Trx or TrxR immunoreactivity and patient survival, which may possibly be related to moderate or intense Trx and TrxR reactivity in most of the cases. Although the Trx system may have an important role in the drug resistance of malignant mesothelioma, these studies also suggest that multiple factors contribute to the promotion, cell proliferation and apoptosis of malignant mesothelioma cells in vivo.
硫氧还蛋白（Trx）与具有氧化还原活性的二硫醇、烟酰胺腺嘌呤二核苷酸磷酸（NADPH）以及硫氧还蛋白还原酶（TrxR）共同构成了一种主要的二硫键还原酶，它可调节细胞的氧化还原状态和细胞增殖，并且可能与恶性细胞的耐药性有关。我们评估了恶性胸膜间皮瘤细胞系、非恶性胸膜间皮以及恶性胸膜间皮瘤活检组织中的Trx系统。在所研究的四个人间皮瘤细胞系中，Trx以及胞质和线粒体TrxR的信使核糖核酸（mRNA）和免疫反应性蛋白均呈阳性。6例组织学上健康的非恶性胸膜间皮未显示Trx或TrxR免疫反应性，而对26例人恶性胸膜间皮瘤活检组织进行的免疫组织化学检查显示，所有病例的Trx均呈阳性，23例（88%）的TrxR呈阳性。在间皮瘤病例中，分别有85%（22例）和61%（14例）检测到Trx或TrxR的中度或强免疫反应性。Trx和TrxR的染色模式主要为弥漫性和细胞质染色，但在39%的间皮瘤病例中也可检测到明显的核染色。尽管在肿瘤细胞中可见Trx和TrxR染色，但在间皮瘤活检组织中，Trx或TrxR表达与肿瘤细胞增殖或凋亡之间未显示出显著相关性。Trx或TrxR免疫反应性强度与患者生存率之间也无显著相关性，这可能与大多数病例中Trx和TrxR呈中度或强反应性有关。尽管Trx系统可能在恶性间皮瘤的耐药性中起重要作用，但这些研究也表明，多种因素在体内促进恶性间皮瘤细胞的增殖和凋亡。
