Suppression of the malignant phenotype in human pancreatic cancer cells by the overexpression of manganese superoxide dismutase.
Suppression of the malignant phenotype in human pancreatic cancer cells by the overexpression of manganese superoxide dismutase.
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DOI：
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发表时间：
2003-04
影响因子：
5.7
通讯作者：
C. Weydert;B. Roling;Jingru Liu;M. Hinkhouse;J. Ritchie;L. Oberley;J. Cullen
中科院分区：
文献类型：
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作者：
C. Weydert;B. Roling;Jingru Liu;M. Hinkhouse;J. Ritchie;L. Oberley;J. Cullen
细胞含有大量的抗氧化剂，可以预防或修复活性氧造成的损伤。抗氧化系统的一个组成部分，锰超氧化物歧化酶（MnSOD），位于线粒体中，这种蛋白质的水平先前已被证明与胰腺癌细胞的生长呈负相关。本研究的目的是确定 MnSOD 过度表达是否可以抑制人胰腺癌细胞系的体外和体内恶性表型。通过检查软琼脂中的细胞生长、铺板效率和不依赖贴壁的生长，确定胰腺癌细胞系 MIA PaCa-2 中的肿瘤细胞行为。通过腺病毒-MnSOD 构建体的感染，MnSOD 在胰腺癌细胞系 MIA PaCa-2 中过度表达。细胞也被皮下注射。在裸鼠中并计算肿瘤体积。将腺病毒 MnSOD 构建体（10(9) 噬斑形成单位）单次和多次直接注射至肿瘤。用腺病毒-MnSOD 构建体转导后，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、铺板效率和软琼脂中的生长均下降。与亲代细胞系相比，注射腺病毒 MnSOD 构建体的裸鼠肿瘤生长缓慢，存活率增加，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存活期。这些结果表明MnSOD可能是人类胰腺癌的抑癌基因。 MnSOD 基因的传递可能有利于抑制胰腺癌的生长。
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.