Li N, Oberley T D, Oberley L W, Zhong W
Department of Pathology and Laboratory Medicine, University of Wisconsin Medical School, Madison, USA.
Prostate. 1998 May 15;35(3):221-33. doi: 10.1002/(sici)1097-0045(19980515)35:3<221::aid-pros8>3.0.co;2-j.
Recent studies suggest that the gene for manganese superoxide dismutase (MnSOD) is a candidate tumor-suppressor gene. The present study was designed to study the effect of overexpression of MnSOD on cultured human prostate carcinoma cells.
DU145 human prostate carcinoma cells were transfected with the cDNA for manganese superoxide dismutase (MnSOD), and two clones overexpressing MnSOD activity were subsequently characterized by comparison with parental and plasmid control-transfected cells.
One clone overexpressing MnSOD had no change in other antioxidant enzymes (AEs) (nonadapted), while a second clone showed an increase in catalase activity (adapted). Sensitivity of parental, plasmid control-transfected, and MnSOD cDNA-transfected cells to agents that generate oxidative stress correlated with AE profiles. Both clones overexpressing MnSOD activity showed increased reactive oxygen species levels under basal cell culture conditions. Both clones overexpressing MnSOD activity showed inhibition of cell growth in vitro and in vivo compared with parental and plasmid control-transfected cells. Flow cytometry studies using mitochondrial-specific probes showed equal mitochondrial mass in all cell lines, but altered mitochondrial membrane potential in MnSOD-overexpressing clones compared with parental or plasmid control-transfected cells.
Our results suggest novel mechanisms by which MnSOD overexpression may modulate the malignant phenotype, with potential applications in developing new therapies for prostate cancer.
近期研究表明，锰超氧化物歧化酶（MnSOD）基因是一种候选肿瘤抑制基因。本研究旨在探讨MnSOD过表达对培养的人前列腺癌细胞的影响。
用锰超氧化物歧化酶（MnSOD）的cDNA转染DU145人前列腺癌细胞，随后通过与亲本细胞和质粒对照转染细胞比较，对两个过表达MnSOD活性的克隆进行表征。
一个过表达MnSOD的克隆在其他抗氧化酶（AE）方面无变化（未适应），而另一个克隆的过氧化氢酶活性增加（适应）。亲本细胞、质粒对照转染细胞和MnSOD cDNA转染细胞对产生氧化应激的试剂的敏感性与AE谱相关。两个过表达MnSOD活性的克隆在基础细胞培养条件下均显示活性氧水平升高。与亲本细胞和质粒对照转染细胞相比，两个过表达MnSOD活性的克隆在体外和体内均显示出细胞生长受到抑制。使用线粒体特异性探针的流式细胞术研究表明，所有细胞系中的线粒体质量相等，但与亲本或质粒对照转染细胞相比，MnSOD过表达克隆中的线粒体膜电位发生了改变。
我们的结果提示了MnSOD过表达可能调节恶性表型的新机制，在开发前列腺癌新疗法方面具有潜在应用价值。
