TY - JOUR AB - 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. AD - Department of Hematology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China Department of Public Health Sciences, University of Rochester, Rochester, NY 14642, USA Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China AU - Tang,Hailong AU - Xu,Li AU - Cen,Xi AU - Yang,Li AU - Feng,Juan AU - Li,Guang AU - Zhu,Huafeng AU - Gao,Shan AU - Yu,Yan AU - Zhao,Yaping AU - Tian,Zhiqiang AU - Hou,Liping AU - Yu,Shuchun AU - Gao,Guangxun DA - 2020/06/01 DO - 10.3892/ijmm.2020.4553 EP - 1672 IS - 6 JO - Int J Mol Med KW - multiple myeloma cyclin dependent kinase 5 prognosis bortezomib NF‑κB pathway synergistic effect PY - 2020 SN - 1107-3756 1791-244X SP - 1661 ST - CDK5 inhibition in vitro and in vivo induces cell death in myeloma and overcomes the obstacle of bortezomib resistance T2 - International Journal of Molecular Medicine TI - CDK5 inhibition in vitro and in vivo induces cell death in myeloma and overcomes the obstacle of bortezomib resistance UR - https://doi.org/10.3892/ijmm.2020.4553 VL - 45 ER -