Lewis Anne, Du Juan, Liu Jingru, Ritchie Justine M, Oberley Larry W, Cullen Joseph J
University of Iowa College of Medicine, Iowa City, 52242, USA.
Clin Exp Metastasis. 2005;22(7):523-32. doi: 10.1007/s10585-005-4919-7. Epub 2006 Feb 11.
Pancreatic cancer has a dismal prognosis due to the fact that patients present late when metastatic disease is already present. Previous studies have demonstrated that pancreatic cancer cells have decreased levels of MnSOD, which correlates well with increased rates of tumor cell proliferation. Recently, we have found that nude mice injected with MIA PaCa-2 human pancreatic cancer cells in the flank occasionally develop ascites and intra-abdominal metastatic deposits. Mice that developed ascites were sacrificed and the ascites cultured. Necropsy demonstrated metastatic tumors in the retroperitoneum, which were excised, digested, and cultured. Western blots, enzyme activity and enzyme activity gels were performed for manganese superoxide dismutase (MnSOD), copper/zinc (CuZnSOD), catalase, and glutathione peroxidase (GPx) in the ascites cell line, metastatic tumor cell line, MIA PaCa-2 primary pancreatic cancer cell line, and the Capan-1, a metastatic pancreatic cancer cell line. Cell growth, plating efficiency, growth in soft agar and growth in nude mice were determined in the ascites, metastatic tumor, and MIA PaCa-2 cell lines. MnSOD, CuZnSOD, and GPx protein and activity were increased in the ascites, metastatic tumor, and Capan-1 cell lines compared to MIA PaCa-2. The ascites and metastatic tumor cell lines had decreased cell growth, plating efficiency, and growth in soft agar, but the ascites cell line had increased cell growth in 4 and 1% O(2) concentrations in vitro and more rapid growth in vivo. Metastatic disease is associated with changes in the content and activity of antioxidant enzymes with an associated change in growth characteristics depending on the O(2) concentrations.
由于患者在出现转移性疾病时才就诊较晚，胰腺癌的预后很差。先前的研究表明，胰腺癌细胞中锰超氧化物歧化酶（MnSOD）水平降低，这与肿瘤细胞增殖率增加密切相关。最近，我们发现，在侧腹注射MIA PaCa-2人胰腺癌细胞的裸鼠偶尔会出现腹水和腹腔内转移性沉积物。对出现腹水的小鼠实施安乐死并培养腹水。尸检显示腹膜后有转移性肿瘤，将其切除、消化并培养。对腹水细胞系、转移性肿瘤细胞系、MIA PaCa-2原发性胰腺癌细胞系以及转移性胰腺癌细胞系Capan-1进行了锰超氧化物歧化酶（MnSOD）、铜/锌超氧化物歧化酶（CuZnSOD）、过氧化氢酶和谷胱甘肽过氧化物酶（GPx）的蛋白质免疫印迹、酶活性和酶活性凝胶分析。测定了腹水、转移性肿瘤和MIA PaCa-2细胞系的细胞生长、接种效率、软琼脂中生长情况以及裸鼠体内生长情况。与MIA PaCa-2相比，腹水、转移性肿瘤和Capan-1细胞系中MnSOD、CuZnSOD和GPx的蛋白质及活性增加。腹水和转移性肿瘤细胞系的细胞生长、接种效率以及软琼脂中生长情况降低，但腹水细胞系在体外4%和1%氧气浓度下细胞生长增加，且在体内生长更快。转移性疾病与抗氧化酶的含量和活性变化相关，其生长特征的相关变化取决于氧气浓度。
