Teoh Melissa L T, Sun Wenqing, Smith Brian J, Oberley Larry W, Cullen Joseph J
Department of Surgery and Radiation Oncology, University of Iowa College of Medicine, Iowa City, IA 52242, USA.
Clin Cancer Res. 2007 Dec 15;13(24):7441-50. doi: 10.1158/1078-0432.CCR-07-0851.
The aim of the present study was to compare the effects of the three different forms of the antioxidant enzyme superoxide dismutase [i.e., manganese superoxide dismutase (MnSOD), copper zinc superoxide dismutase (CuZnSOD), and extracellular superoxide dismutase (EcSOD)] on the malignant phenotype of human pancreatic cancer.
Human pancreatic cancer cell lines were infected with adenoviral vectors containing the cDNAs for three different forms of the antioxidant enzyme SOD. Intratumoral injections of the adenoviral vectors were used in nude mice with human tumor xenografts.
Increases in immunoreactive protein and enzymatic activity were seen after infections with the AdMnSOD, AdCuZnSOD, or AdEcSOD constructs. Increased SOD activity decreased superoxide levels and increased hydrogen peroxide levels. Increasing SOD levels correlated with increased doubling time. Cell growth and plating efficiency decreased with increasing amounts of the adenoviral constructs, with the AdCuZnSOD vector having the greatest effect in decreasing in vitro tumor growth. In contrast, inhibiting endogenous SOD with small interfering RNA increased superoxide levels and promoted tumor growth. Of the three SODs, tumors grew the slowest and survival was increased the greatest in nude mice injected with the AdEcSOD construct.
Scavenging plasma membrane-generated superoxide may prove beneficial for suppression of pancreatic cancer growth.
本研究旨在比较三种不同形式的抗氧化酶超氧化物歧化酶[即锰超氧化物歧化酶（MnSOD）、铜锌超氧化物歧化酶（CuZnSOD）和细胞外超氧化物歧化酶（EcSOD）]对人胰腺癌恶性表型的影响。
用人胰腺癌细胞系感染含有三种不同形式抗氧化酶SOD cDNA的腺病毒载体。将腺病毒载体瘤内注射到有人肿瘤异种移植的裸鼠体内。
用AdMnSOD、AdCuZnSOD或AdEcSOD构建体感染后，免疫反应性蛋白和酶活性增加。超氧化物歧化酶活性增加可降低超氧化物水平并增加过氧化氢水平。超氧化物歧化酶水平升高与倍增时间增加相关。随着腺病毒构建体数量的增加，细胞生长和平板接种效率降低，其中AdCuZnSOD载体对体外肿瘤生长的抑制作用最大。相反，用小干扰RNA抑制内源性超氧化物歧化酶可增加超氧化物水平并促进肿瘤生长。在三种超氧化物歧化酶中，注射AdEcSOD构建体的裸鼠肿瘤生长最慢，生存期延长最多。
清除质膜产生的超氧化物可能对抑制胰腺癌生长有益。
