Do statins improve the effect of bortezomib in myeloma treatment?

Objective- hypothesis: There is still a need for agents that affect new and different pathways due to the incurability of the disease. Considering that malignant diseases are less common in patients using statins, in this study, it was investigated whether the effect of statins, which act on the mevalonate pathway, which is responsible for cholesterol synthesis and plays an important role in cell proliferation, together with bortezomib, will contribute to the treatment of the disease. It was aimed to examine the effects of statins on plasma cells when used together with bortezomib in MM cell culture. Method: U266 myeloma cell line was used in the study. Cells were grown in RPMI 1640 medium in %10 heat-inactivated Fetal Bovine Serum, 100 U/ml penicillin, 100 mg/ml streptomycin, 200 mM L-glutamine and %5 CO2, 37 oC atmosphere and 75 cm2 polystyrene flasks. IC50 values of bortezomib and atorvastatin were determined. Viability with MTS/PMS assay and apoptosis with Annexin V-FITC were evaluated by administering the determined doses of bortezomib, atovastatin and combined drug Results: Viability decreased in bortezomib, atorvastatin and combined drug groups with MTS/PMS experiment. In the flow cytometry experiment, a statistically significant difference was found in the combined drug group in terms of apoptosis compared to the bortezomib group alone (p=0.008). Conclusion: As a result of the study, a decrease in viability and induction of apoptosis were observed in the U266 MM cell line with atorvastatin. However, when bortezomib and atorvastatin used in the treatment of MM were administered together, it was found that bortezomib increased its effectiveness. Further in vitro studies with different statins in different MM cell lines will guide phase III studies.