Lovastatin and thalidomide have a combined effect on the rate of multiple myeloma cell apoptosis in short term cell cultures

Abstract

Multiple myeloma is characterized by an accumulation of plasma cells in bone marrow. Despite many therapeutic regimens introduced recently, the prognosis for patients suffering from treatment-resistant or relapsing multiple myeloma is still very poor. Thus, there is an urgent medical need for novel innovative drugs. Thalidomide is successfully used in resistant or relapsing myeloma patients, being reported to induce apoptosis or G1 growth arrest of myeloma cells and to regulate microvessel density and cytokine secretion. Lovastatin, largely used for the treatment of hypercholesterolemia, is another promising drug in multiple myeloma. High doses of lovastatin have been shown to have antiproliferative effect by inhibition of malignant cell proliferation and inducing programmed cell death. In this study, we tried to assess whether thalidomide and lovastatin had a combined effect on apoptosis of myeloma cells. We analyzed apoptosis induced by mixture of these two drugs in short-term cell culture of myeloma plasmocytes. To assess apoptosis, we used Annexin V and propidium iodide binding. We also examined the regulation of BCL-2 and BAX protein expression in the population of CD138+ plasmocytes. The cells were analyzed with the use of flow cytometry technique. The experiments were done before and after 72 h of cell culture. We detected a higher rate of apoptosis induced by lovastatin and thalidomide mixture in comparison to apoptosis induced by lovastatin or thalidomide alone. In most patients, the BCL-2/BAX ratio was lower in cell cultures supplemented with mixture of lovastatin and thalidomide in comparison with cell cultures supplemented with lovastatin or thalidomide alone. Based on our research we conclude that the mixture of lovastatin and thalidomide may increase the rate of multiple myeloma cells apoptosis in comparison to the single drug and the precise mechanism of this effect should be approved by further research.