ArticleInternational journal of molecular medicine2020
CDK5 inhibition in vitro and in vivo induces cell death in myeloma and overcomes the obstacle of bortezomib resistance.
Article in International journal of molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 11 citations in OpenAlex.
- Integrative Network Analysis of Single-Cell RNA Findings and a Priori Knowledge Highlights Gene Regulators in Multiple Myeloma Progression.International journal of molecular sciences · 2026Article
- A patent review of cyclin-dependent kinase 5 (CDK5) inhibitors (1999-2025).Frontiers in bioengineering and biotechnology · 2026Review
- Different Strategies to Overcome Resistance to Proteasome Inhibitors-A Summary 20 Years after Their Introduction.International journal of molecular sciences · 2024Review
- Cyclin-dependent kinase 5 (CDK5) inhibitors in Parkinson disease.Journal of cellular and molecular medicine · 2024Review
- CDK5: an oncogene or an anti-oncogene: location location location.Molecular cancer · 2023Review
- Rational drug combination design in patient-derived avatars reveals effective inhibition of hepatocellular carcinoma with proteasome and CDK inhibitors.Journal of experimental & clinical cancer research : CR · 2022Article
- CDK9 inhibitors in multiple myeloma: a review of progress and perspectives.Medical oncology (Northwood, London, England) · 2022Review
- Silencing of kallikrein-related peptidase 6 attenuates the proliferation, migration, and invasion of gastric cancer cells through inhibition of epithelial-mesenchymal transition.Experimental and therapeutic medicine · 2021Article
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The emergence of new drugs is a major feature of the treatment history of multiple myeloma (MM), which also reflects the current incurability of MM. As a unique member of cyclin dependent kinase (CDK) family, CDK5 participates in numerous tumorigenic or non‑tumorigenic processes. The aim of this study is to investigate the effects of CDK5 on the viability of MM cells and bortezomib resistance using western blotting, immunohistochemistry, transient transfection, MTT assays, cell cycle analysis, apoptosis assays and a myeloma xenograft mouse model. The present study found that MM patients with high CDK5 expression in the bone marrow do not respond well to bortezomib, have higher DS stage and worse prognosis. Genetic and pharmacological (dinaciclib) inhibition of CDK5 triggers MM cell viability inhibition. Dinaciclib induces G2/M arrest and apoptosis of MM cells. In vivo experiments with myeloma xenograft mice indicate that dinaciclib significantly reduces the volume of tumors with good tolerance. Dinaciclib combined with bortezomib exerts a synergistic anti‑myeloma activity accompanied by inhibiting the activation of the nuclear factor‑κB pathway. This study demonstrates the important role of CDK5 in the pathogenesis, viability, prognosis and resistance to bortezomib of MM, laying a solid theoretical foundation for further clinical use of CDK5 inhibitors.
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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.