Does metformin increase the efficacy of lenalidomid in myeloma treatment?

Objective-hypothesis: There has been a considerable improvement in Multiple Myeloma treatment following the use of immunomodulators and proteasome inhibitors in the year 2000. Even though they considerably prolong life, these drugs do not offer a definite treatment. Previous studies have shown the anti-myeloma activity of metformin. Using in vitro method, this study investigates the impact of metformin, which is a cheap drug with relatively fewer side effects, on vitality and apoptosis of myeloma cell lines and whether it potentiates the effect of lenalidomide that is widely used to treat myeloma. Method: The study made use of the U266 myeloma cell line. The cells were grown in RPMI 1640 medium with 10% heat inactivated Fetal Bovine Serum, 100 U/ml penicillin, 100 mg/ml streptomycin, L-glutamine in 200 mM medium and 5% CO2 at 37°C atmosphere and in 75 mL polystyrene flasks. The cells grown were administered various doses of metformin and lenalidomide and IC50 values for both drugs were identified. Identified doses of metformin, lenalidomide and a combination of these two were administered and the vitality and apoptosis were investigated using MTS/PMS and Annexin V-FITC, respectively. Results: The MTS/PMS experiment showed that vitality decreased in metformin, lenalidomide and combination groups. The vitality was lower in wells that were administered metformin only and combination drugs compared to ones only administered lenalidomid, however, this difference was not statistically significant (p=0,48 and p=0,32, respectively). Significant apoptosis was identified in the metformin group compared to the control group in the flow cytometry experiment (p<0,001). No difference was found between the combined group and the lenalidomide group (p=0,39). Conclusion: The study identified a reduction in vitality and induction in apoptosis in myeloma cell lines due to metformin. On the other hand, it was revealed that in combined administration, metformin did not improve the efficacy of lenalidomide. Further studies with metformin would be beneficial in the treatment of Multiple Myeloma. Keywords: Metformin, Multiple Myeloma, Lenalidomide Contact address: ersinncakir@gmail.com