Wang J.,Center for Cancer Biology Pathology Site |
Wang J.,University of Adelaide |
Hughes T.P.,Center for Cancer Biology Pathology Site |
Hughes T.P.,University of Adelaide |
And 12 more authors.
British Journal of Cancer | Year: 2012
Background: The human organic cation transporter-1 (OCT-1) is the primary active protein for imatinib uptake into target BCR-ABL-positive cells. Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used by chronic myeloid leukaemia (CML) patients on imatinib to manage musculoskeletal complaints. Methods: Here we investigated the impact of NSAIDs on functional activity of the OCT-1 (OCT-1 activity; OA) in CML cells.Results:Although ten of twelve NSAIDs tested had no significant impact on OA (P=0.05), we observed increased OA (27% increase in K562; 22% increase in KU812 cells, P=0.05) and reduced IC50 imatinib when treated with diclofenac. Co-incubation with imatinib and diclofenac resulted in a significantly lower viable cell number compared with imatinib alone. In contrast, ibuprofen led to a significant decrease in OA, an increase in IC50 imatinib and thus reduced the cytotoxicity of imatinib. In primary CML samples, diclofenac significantly increased OA, particularly in patients with low OA (<4 ng per 200 000 cells), and significantly decreased IC50 imatinib. Ibuprofen induced significant decreases in OA in CML samples and healthy donors. Conclusion: On the basis of the expected impact of these two drugs on OA, ibuprofen should be avoided in combination with imatinib. Further studies are warranted regarding the potential benefit of diclofenac to improve OA in a clinical setting. © 2012 Cancer Research UK.