MLN-0905

Multiple myeloma (MM) is a prevalent bone marrow cancer that often presents challenges due to treatment resistance. This study assessed the apoptotic and antiproliferative effects of the Polo-like kinase 1 inhibitor MLN0905, alone and in combination with lenalidomide, in an MM cell line. The AMO1 human MM cell line was treated with various doses of lenalidomide, MLN0905, or their combination. Cell viability was assessed via the MTT assay, and apoptosis was quantified via Annexin V/propidium iodide staining. The effects of treatment on BCL2, p21, and PUMA gene expression were evaluated through quantitative real-time polymerase chain reaction. The IC50 values were 50.61 μM for lenalidomide and 54.27 nM for MLN0905, indicating dose-dependent cytotoxic effects. When 30 μM lenalidomide was combined with 50 nM MLN0905, the percentage of apoptotic cells increased to 51.31%. The SynergyFinder platform identified optimal synergy at 40 μM lenalidomide plus 50 nM MLN0905. MLN0905 significantly reduced p21, PUMA, and BCL2 mRNA levels, whereas lenalidomide increased p21 and PUMA mRNA expression and decreased BCL2 expression. The combination treatment notably increased p21 expression and significantly reduced BCL2 levels, with no marked change in PUMA mRNA. This study revealed that MLN0905 significantly affects AMO1 cell survival, reducing the mRNA expression of genes involved in apoptosis and the cell cycle in a dose-dependent manner. Furthermore, the combination of lenalidomide and MLN0905 synergistically decreases cell survival and induces apoptosis in AMO1 cells. The altered expression of apoptotic genes highlights the potential of this drug combination for future multiple myeloma research.