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<p>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 <i>BCL2</i>, <i>p21</i>, and <i>PUMA</i> gene expression were evaluated through quantitative real-time polymerase chain reaction. The IC50 values were 50.61&#xa0;μM for lenalidomide and 54.27&#xa0;nM for MLN0905, indicating dose-dependent cytotoxic effects. When 30&#xa0;μM lenalidomide was combined with 50&#xa0;nM MLN0905, the percentage of apoptotic cells increased to 51.31%. The SynergyFinder platform identified optimal synergy at 40&#xa0;μM lenalidomide plus 50&#xa0;nM MLN0905. MLN0905 significantly reduced <i>p21</i>, <i>PUMA</i>, and <i>BCL2</i> mRNA levels, whereas lenalidomide increased <i>p21</i> and <i>PUMA</i> mRNA expression and decreased <i>BCL2</i> expression. The combination treatment notably increased <i>p21</i> expression and significantly reduced <i>BCL2</i> levels, with no marked change in <i>PUMA</i> 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.</p> Graphical abstract <p>MLN0905, a potent PLK1 inhibitor, synergizes with lenalidomide to promote apoptosis and suppress survival in multiple myeloma. This combination modulates critical apoptotic and cell cycle gene expression, highlighting a promising therapeutic strategy for overcoming resistance in multiple myeloma treatments.</p> <p></p>

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MLN0905, a new inhibitor of Polo-like kinase 1 (PLK1), enhances the efficiency of lenalidomide in promoting the apoptosis of multiple myeloma cell lines

  • 期刊论文

  • 发表日期：

    2025年4月25日

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  • Reyhane Piri,
  • Minoo Shahidi,
  • Zahra Pooraskari,
  • Sina Habibi

摘要

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.

Graphical abstract

MLN0905, a potent PLK1 inhibitor, synergizes with lenalidomide to promote apoptosis and suppress survival in multiple myeloma. This combination modulates critical apoptotic and cell cycle gene expression, highlighting a promising therapeutic strategy for overcoming resistance in multiple myeloma treatments.