Abstract
Background: Aerosolized cyclosporine A (CsA) increases the local concentration of CsA in lung tissue and has proven to be an effective therapy for refractory rejection in lung transplant patients. However, the safety of high concentrations of CsA on tumour progression remains controversial. Materials and Methods: Human lung adenocarcinoma A549 cells were cultured with or without 1-3 μg/ml of CsA. The percentage of apoptotic cells was evaluated by Annexin V staining. The expressions of caspase-3, -9, -8 and cytochrome c were determined by Western blotting. Results: CsA therapy suppressed the growth of human lung cancer cells and increased the percentage of apoptotic cells compared with control cells. Western blot analysis revealed that CsA increased the levels of cytosolic cytochrome c and cleaved caspase-3 and -9, but not of cleaved caspase-8 in the lung cancer cells, suggesting that CsA-induced apoptosis is associated with the activation of caspase-3 and -9. Conclusion: Our findings indicate that a high concentration of CsA has cytocidal effects through the caspase-3- and -9-dependent apoptotic pathway. This result shows that local administration of CsA does not increase the risk of secondary lung cancer.
- Received April 3, 2011.
- Revision received May 26, 2011.
- Accepted May 27, 2011.
- Copyright© 2011 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved