Metastatic progression of pancreatic cancer: Changes in antioxidant enzymes and cell growth
Metastatic progression of pancreatic cancer: Changes in antioxidant enzymes and cell growth
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DOI：
10.1007/s10585-005-4919-7
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发表时间：
2005-11-01
影响因子：
4
通讯作者：
Cullen, JJ
中科院分区：
文献类型：
--
作者：
Lewis, A;Du, J;Cullen, JJ
胰腺癌的预后很差，这是因为当转移性疾病已经存在时，患者出现的时间较晚。先前的研究表明，胰腺癌细胞具有降低的MnSOD水平，这与肿瘤细胞增殖速率的增加密切相关。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。处死产生腹水的小鼠并培养腹水。尸检显示腹膜后转移性肿瘤，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和Capan-1转移性胰腺癌细胞系中的锰超氧化物歧化酶（MnSOD）、铜/锌（CuZnSOD）、过氧化氢酶和谷胱甘肽过氧化物酶（GPx）进行蛋白质印迹、酶活性和酶活性凝胶。在腹水、转移性肿瘤和MIA PaCa-2细胞系中测定细胞生长、平板接种效率、软琼脂生长和裸鼠生长。MnSOD，CuZnSOD，GPx蛋白和活性增加腹水，转移性肿瘤，Capan-1细胞系相比，MIA PaCa-2。腹水和转移性肿瘤细胞系的细胞生长，铺板效率，并在软琼脂中的生长下降，但腹水细胞系在4和1%O-2浓度在体外细胞生长增加，在体内生长更快。转移性疾病与抗氧化酶的含量和活性的变化相关，并且与依赖于O-2浓度的生长特性的相关变化相关。
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.