科研之友
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摘要
Chemotherapeutic failure and metastasis are the main causes of high mortality rate in lung cancer. Alteration of cellular redox status in response to endogenous stimuli or exogenous compounds has a significant impact on cell signaling and behavior. Herein we divulge for the first time that lung cancer cells exposed to a-lipoic acid (LA) resulted in a higher level of cellular superoxide anion (O-2(center dot-)) and hydrogen peroxide (H2O2), and such an increase of the specific reactive oxygen species (ROS) downregulated integrin beta 1 and beta 3, the integrins known for potentiating aggressive behavior and metastasis. The LA-treated cells exhibited significant decrease in their abilities to survive in detached condition and grow in anchorage-independent soft agar assay. Furthermore, LA sensitized the cells to cisplatin, etoposide and paclitaxel-induced apoptosis. For underlying mechanism, we found that the treatment of the cells with LA significantly decreased integrin beta 1 and beta 3, while had no effect on integrin alpha 5 and ay. Interestingly, survival protein p-AKT and anti-apoptotic protein Bcl-2 were reduced in an association to such integrin modulations. Using ROS probes and selective anti-oxidants, we have shown that H2O2 and O-2(center dot-) induced by LA are key players for the decrease of beta 1 and beta 3 integrins, respectively. These findings indicate a novel effect of LA as well as specific ROS, O-2(center dot-) and H2O2 in integrin regulation, anoikis and chemotherapeutic sensitizations.
