In vitro comparison of the cytotoxic effects of lenalidomide alone and in combination with verapamil on myeloma cell line

Abstract

Introduction Multiple myeloma (MM) is a malignant hematological disease characterized by monoclonal proliferation of plasma cells. High-dose chemotherapy with novel agents and autologous stem cell transplantation are options for treatment. However, MM treatment generally results in failure. The most important reason for this failure is the resistance to chemotherapeutic drugs. Various studies have been tried to combine chemosensitizer agents that increase the cytotoxic effects of the chemotherapeutics to eliminate the drug resistance. In our study, we aimed to evaluate the effect of verapamil on the cytotoxic effect of lenalidomide on the myeloma cell line. Materials and methods Verapamil is a chemosensitizer that suppresses the P-glycoprotein. In our study, lenalidomide, an immunomodulatory agent, was compared alone and in combination with verapamil for cytotoxic effects. U266 MM cell line was used in the study. At the concentrations of 0.001, 0.01, 0.1, 1, 10, 50, and 100 µM, lenalidomide alone and the combination of lenalidomide at the same concentrations with 2.5 µg/ml of verapamil were compared in terms of possible cytotoxic properties. Cell viability was measured by XTT (2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide) test. Results A statistically significant decrease in the inhibitor concentration, causing 50% decrease in cell proliferation (IC50) of lenalidomide, was provided via verapamil administration. Our study revealed that the cytotoxic effect of lenalidomide increases when combined with verapamil. Conclusion We aimed to understand whether the cytotoxic effect of lenalidomide, which has an important place in the treatment of MM, can be increased with an easily available drug such as verapamil. We think that more studies and meta-analyses are needed owing to the different results related to the subject in the literature, and we hope to set an example for new studies.