Evidence map›Paper›PMID 40278989›Full record

ArticleInvestigational new drugs2025

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

Reyhane Piri, Minoo Shahidi, Zahra Pooraskari, Sina Habibi

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Article in Investigational new drugs, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Reyhane PiriDepartment of Hematology and Blood Banking, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran.
Minoo ShahidiDepartment of Hematology and Blood Banking, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran. Shahidi.minoo@gmail.com.
Zahra PooraskariDepartment of Hematology and Blood Banking, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran.ORCID 0009-0009-5339-7180
Sina HabibiDepartment of Hematology and Blood Banking, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran.ORCID 0000-0003-1183-8549

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

Antineoplastic AgentsApoptosisCell Cycle ProteinsLenalidomideMultiple MyelomaProtein Kinase InhibitorsProtein Serine-Threonine KinasesProto-Oncogene ProteinsPteridinesThalidomideApoptosis Regulatory ProteinsCell Line, TumorCell ProliferationCell SurvivalCyclopentanesDrug SynergismAntineoplastic AgentsApoptosis Regulatory ProteinsBBC3 protein, humanCell Cycle ProteinsCyclopentanesLenalidomidepevonedistatPolo-Like Kinase 1Protein Kinase InhibitorsProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-bcl-2PteridinesPyrimidinesThalidomideApoptosisLenalidomideMLN0905Multiple myelomaPolo-like kinase 1

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.