Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Phatumwan, Bangkok, Thailand 10330.
Anticancer Res. 2012 Feb;32(2):483-90.
Oxidative stress has been shown to play an important role in cancer progression. In lung cancer, increasing expression of caveolin-1 (Cav-1) has been found in both primary and metastatic carcinomas and may be critical in the regulation of the oxidative status of cancer cells.
Using molecular and pharmacological manipulations, the role of Cav-1 in regulating cellular oxidative status in lung cancer cells was investigated. The level of Cav-1 was determined by western blot analysis and reactive oxygen species (ROS) were detected by specific fluorescence probes.
The treatment of lung cancer H460 cells with hydrogen peroxide (H(2)O(2)) significantly up-regulated ROS inside the cells and contributed to cell apoptosis. While cells stably transfected with Cav-1 overexpressing plasmids (H460/Cav-1) exhibited decreased ROS signal and attenuated cell death rate, shRNACav-1 transfected (H460/shCav-1) cells showed enhanced ROS signal and increased cell damage. The use of specific superoxide anion and the hydrogen peroxide detecting assays and hydroxyl radical inhibition assay indicated that the variable oxidative stress found in these cells was mainly due to the alteration of the cellular hydroxyl radical level.
A novel role of Cav-1 protein is the suppression of cellular oxidative stress induced by H(2)O(2).
氧化应激在癌症进展中起着重要作用。在肺癌中，已发现原代和转移性癌中 Cav-1（小窝蛋白-1）的表达增加，这可能对癌细胞的氧化状态调节至关重要。
使用分子和药理学操作，研究 Cav-1 在调节肺癌细胞中细胞氧化状态中的作用。通过 Western blot 分析测定 Cav-1 的水平，并用特异性荧光探针检测活性氧（ROS）。
用过氧化氢（H2O2）处理肺癌 H460 细胞可显著上调细胞内的 ROS，促进细胞凋亡。而用 Cav-1 过表达质粒（H460/Cav-1）稳定转染的细胞表现出降低的 ROS 信号和减弱的细胞死亡率，而 shRNACav-1 转染的（H460/shCav-1）细胞则表现出增强的 ROS 信号和增加的细胞损伤。使用特定的超氧阴离子和过氧化氢检测试剂盒以及羟基自由基抑制测定法表明，这些细胞中发现的可变氧化应激主要是由于细胞内羟基自由基水平的改变。
Cav-1 蛋白的一个新作用是抑制 H2O2 诱导的细胞氧化应激。
