Weydert Christine, Roling Benjamin, Liu Jingru, Hinkhouse Marilyn M, Ritchie Justine M, Oberley Larry W, Cullen Joseph J
Department of Radiation Oncology, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA.
Mol Cancer Ther. 2003 Apr;2(4):361-9.
Cells contain a large number of antioxidants to prevent or repair the damage caused by reactive oxygen species. One component of the antioxidant system, manganese superoxide dismutase (MnSOD), is localized in the mitochondria, and the levels of this protein have been previously shown to inversely correlate with pancreatic cancer cell growth. The aim of the present study was to determine whether MnSOD overexpression could suppress the in vitro and in vivo malignant phenotype of a human pancreatic cancer cell line. Tumor cell behavior was determined in the pancreatic cancer cell line MIA PaCa-2 by examining cell growth, plating efficiency, and anchorage-independent growth in soft agar. MnSOD was overexpressed in the pancreatic cancer cell line MIA PaCa-2 by infection with an adenovirus-MnSOD construct. Cells were also injected s.c. in nude mice and tumor volume was calculated. Single and multiple direct injections of the adenoviral MnSOD construct (10(9) plaque-forming units) were delivered to the tumor. Increases in MnSOD immunoreactivity and activity were seen after transduction with the adenovirus-MnSOD construct. Increasing MnSOD levels correlated with increased doubling time. Cell growth, plating efficiency, and growth in soft agar decreased with increasing amounts of the adenovirus MnSOD construct. Tumors grew slower and survival was increased in nude mice injected with the adenoviral MnSOD construct compared with the parental cell line, whereas multiple injections of the adenoviral MnSOD construct further inhibited tumor cell growth and extended survival. These results suggest that MnSOD may be a tumor suppressor gene in human pancreatic cancer. Delivery of the MnSOD gene may prove beneficial for suppression of pancreatic cancer growth.
细胞含有大量抗氧化剂以预防或修复活性氧物种造成的损伤。抗氧化系统的一个组成部分，锰超氧化物歧化酶（MnSOD），定位于线粒体中，并且先前已表明该蛋白的水平与胰腺癌细胞生长呈负相关。本研究的目的是确定MnSOD过表达是否能抑制人胰腺癌细胞系的体外和体内恶性表型。通过检测细胞生长、接种效率和在软琼脂中的非锚定依赖性生长，在胰腺癌细胞系MIA PaCa-2中确定肿瘤细胞行为。通过用腺病毒-MnSOD构建体感染，在胰腺癌细胞系MIA PaCa-2中过表达MnSOD。细胞也皮下注射到裸鼠体内并计算肿瘤体积。将腺病毒MnSOD构建体（10⁹ 噬斑形成单位）单次和多次直接注射到肿瘤中。用腺病毒-MnSOD构建体转导后，可见MnSOD免疫反应性和活性增加。MnSOD水平的增加与倍增时间的增加相关。随着腺病毒MnSOD构建体数量的增加，细胞生长、接种效率和在软琼脂中的生长减少。与亲本细胞系相比，注射腺病毒MnSOD构建体的裸鼠肿瘤生长较慢且生存期延长，而多次注射腺病毒MnSOD构建体进一步抑制肿瘤细胞生长并延长生存期。这些结果表明MnSOD可能是人类胰腺癌中的一种肿瘤抑制基因。MnSOD基因的传递可能被证明对抑制胰腺癌生长有益。
