Evaluation of the Cytotoxic Effects of Combined Application of Methotrexate and Statins on Green Monkey Kidney Cells

Lipid disorders that lead to cardiovascular diseases are also common with oncology patients. Therefore, this group of patients is exposed to the risk of interaction between the cytostatic drugs applied and statins. Methotrexate is widely used in cancer treatment. However, it is a highly toxic drug. Nephrotoxicity is the most common side effect following the methotrexate therapy. On the other hand, statins are reported to have possible renoprotective effects against drug-induced nephrotoxicity. The aim of this study was to evaluate the cytotoxic effects of the combined application of methotrexate and statins (atorvastatin, rosuvastatin or pravastatin) on the green monkey kidney cells (GMK), using the MTT and LDH assays. The effect of these drugs and their combination on the GMK cells apoptosis was also evaluated using the Cell Death Detection ELISA kit. The results obtained from the cytotoxicity assays suggest an adverse effect of the combined application of methotrexate (5.5 or 16.5 μM) and atorvastatin (100 μM) on the viability of GMK cells. A decrease in the cell viability in this case was attributed to apoptosis. In the study, a significant reduction in the GMK cell viability was also identified in the MTT assay after 24h of incubation with methotrexate in combination with rosuvastatin or pravastatin. However, in the LDH assay, there were no significant changes that clearly indicate the intensification of their cytotoxic effects. The obtained results, especially in the MTT test, demonstrate a negative influence of the combined application of methotrexate and statins on the viability of GMK cells.