Oxidative stress mediates CoCl2-induced prostate tumour cell adhesion:: Role of protein kinase C and p38 mitogen-activated protein kinase
Oxidative stress mediates CoCl2-induced prostate tumour cell adhesion:: Role of protein kinase C and p38 mitogen-activated protein kinase
复制标题
DOI：
10.1111/j.1742-7843.2007.00074.x
复制
发表时间：
2007-07-01
影响因子：
3.1
通讯作者：
Li, Xue-jun
中科院分区：
文献类型：
--
作者：
Lu, Ning;Zhou, Hong;Li, Xue-jun
氯化钴 (CoCl2) 是一种被证明可以稳定缺氧诱导因子 1 的药物，它与各种缺氧反应有关，最近的一些报告将其与肿瘤恶性肿瘤的增加联系起来。在这项研究中，我们观察了 CoCl2 处理后细胞粘附的变化，并分析了前列腺癌细胞系 PC-3 M 细胞中这种适应的潜在机制。我们发现 CoCl2 以剂量依赖性方式增加肿瘤细胞粘附，这与活性氧 (ROS) 的产生相关。当细胞与硫醇还原剂吡咯烷二硫代氨基甲酸酯 (PDTC) 一起孵育时，ROS 的产生和 COCl2 诱导的细胞粘附都被消除。此外，COCl2处理的细胞中p38丝裂原激活蛋白激酶（p38 MAPK）被激活，这可以被PDTC拮抗。当细胞与特异性 p38 MAPK 抑制剂 SB203580 预孵育时，CoCl2 诱导的细胞粘附减弱。此外，蛋白激酶C可以通过激活p38 MAPK来上调细胞粘附。总之，CoCl2 诱导 ROS 产生，从而使细胞处于氧化应激状态并上调细胞粘附； p38 MAPK 和蛋白激酶 C 可以以 ROS 依赖性方式被激活，进而促进 CoCl2 诱导的细胞粘附。
Cobalt chloride (CoCl2), an agent demonstrated to stabilize hypoxia-inducible factor-1, has been associated with various hypoxic responses, and recently, some reports have linked it to increasing tumour malignancy. In this study, we observed the alteration of cell adhesion after CoCl2 treatment and analysed the potential mechanisms responsible for such adaptations in a prostate cancer cell line PC-3 M cell. We found that CoCl2 increased the tumour cell adhesion in a dose-dependent manner, which correlated with reactive oxygen species (ROS) generation. When cells were incubated with the thiol reductive agent pyrrolidine dithiocarbamate (PDTC), both the ROS generation and the COCl2-induced cell adhesion were abolished. Moreover, p38 mitogen-activated protein kinase (p38 MAPK) was activated in COCl2-treated cells, which could be antagonized by PDTC. And when cells were pre-incubated with specific p38 MAPK inhibitor, SB203580, the cell adhesion induced by CoCl2 was diminished. Moreover, the protein kinase C could up-regulate cell adhesion through activating p38 MAPK. In conclusion, CoCl2 induced ROS generation, thereby placing cells under oxidative stress and up-regulating cell adhesion; p38 MAPK and protein kinase C could be activated in a ROS-dependent fashion, which in turn contributed to cell adhesion induced by CoCl2.