In the present study, we evaluated fibrate-mediated potentiation of statin-induced apoptosis in IM-9 human lymphoblasts.
The pro-apoptotic effects of statin and fibrate were measured by flow cytometry with biotin-annexin V, followed by addition of avidin-fluorescein isothiocyanate and propidium iodide. Apoptosis was confirmed using karyopyknotic staining, as well as detection of DNA fragmentation and caspase 3 activation.
Incubation of IM-9 cells with both 0.1 mu mol/L cerivastatin and 200 mu mol/L clofibrate had a synergistic effect compared with 0.1 mu mol/L cerivastatin alone or 200 mu mol/L clofibrate alone. The magnitude of apoptosis induced by various combinations of statins and clofibrate were as follows: cerivastatin (0.1 mu mol/L) + clofibrate (200 mu mol/L) > atorvastatin (0.1 mu mol/L) + clofibrate (200 mu mol/L) > pravastatin (100 mu mol/L) + clofibrate (200 mu mol/L). Other fibrates (bezafibrate and clinofibrate) did not show any synergistic effect. Furthermore, karyopyknotic staining, caspase 3 activation and DNA fragmentation demonstrated synergistic pro-apoptotic effects of statin and fibrate.
The results of the present study suggest that simultaneous treatment with statins and clofibrate could provide improved therapeutic efficacy in leukaemia patients.