Radotinib inhibits multiple myeloma cell proliferation via suppression of STAT3 signaling
Open accessAbstract
Multiple myeloma (MM) is a hematological cancer causing from accumulated abnormal plasma cells. STAT3 overexpression in MM appears to be mediated by a variety of factors, and it may be associated with an adverse prognosis and play a role in microenvironment-dependent treatment resistance. Unfortunately, MM remains an incurable disease, as relapse is very common. Therefore, there is urgent need to develop new treatment options for MM. Radotinib is a novel anti-cancer drug, currently approved in South Korea for the treatment of chronic myeloid leukemia patients. It is an oral, multitargeted inhibitor of receptor tyrosine kinases, including BCR-ABL, c-KIT, PDGFR, and Src family kinases. However, little is known about the effects of radotinib on multiple myeloma cells. However, little is known about the effects of radotinib on multiple myeloma cells. But even tinip almost not known about the impact of multiple myeloma cells. Moreover, nothing is known about how it affects STAT3 and JAK2. In this study, we analyzed the effect of radotinib on multiple myeloma cells. Herein, Moreover, nothing is known about how it. Moreover, not all is known about how the affects STAT3 and JAK2. We investigated the effect of radotinib on the STAT3 signaling pathway in MM cells, including several MM cell lines and mouse models. So we investigated the effect of radotinib on MM cells, including several MM cell lines and mouse models. Interestingly, radotinib induced apoptosis, and inhibited cell proliferation in MM cells including RPMI-8226, MM.1S, U266B1, and IM-9 cells. Moreover, radotinib treatment significantly increased the number Annexin V-positive cells and G0/G1-phase cells. In addition, radotinib treatment in various MM cells strongly suppressed the activity and expression of STAT3 and JAK2 proteins. We also observed that diverse proteins related to the STAT3 signaling pathway, including c-Myc, Bcl-xL, Mcl-1, cyclin D1 and cyclin D3, were powerfully inhibited by radotinib treatment in MM cells. Furthermore, radotinib significantly suppressed MM cell growth in a xenograft animal model using IM-9 cells. In conclusion, radotinib may play an important role as a candidate agent for MM treatment.
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The pathogenesis of multiple myeloma involves interaction between MM cells and the bone marrow microenvironment through soluble cytokines and cell adhesion molecules, activating PI3K/AKT/mTOR, RAS/MAPK, JAK/STAT, Wnt/β-catenin, and NF-κB pathways.
“The pathogenesis of MM involves the interaction between MM cells and the bone marrow microenvironment through soluble cytokines and cell adhesion molecules, which activate various signaling pathways such as PI3K/AKT/mTOR, RAS/MAPK, JAK/STAT, Wnt/β-catenin, and NF-κB pathways.”
From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [33]
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- Authors
- Heo, S.-K., Noh, E.-K., Seo, H. J., Lee, Y. J., Koh, S., Min, Y. J., Choi, Y., & Jo, J.-C.
- Affiliations
- University of Ulsan (KR)
- Corresponding author
- Jo, Jae-Cheol
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2022-05-03
- Volume
- 17
- Issue
- 5
- Pages
- e0265958
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC9064077
- OpenAlex
- W4229370502
- Cited by
- 11
- References
- 36
- Citations by year
- 2026: 1 · 2024: 6 · 2023: 3 · 2022: 1
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Ulsan University Hospital (UUH-2021-07, 2022-UUHBRI-01)
- National Research Foundation of Korea (NRF-2021R1F1A1050975, NRF-2017R1A1A3A04069314)
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Keywords
- radotinib, multiple myeloma, STAT3 signaling, JAK2, receptor tyrosine kinase inhibitors, cell proliferation inhibition, apoptosis, cell cycle arrest, c-Myc, Bcl-xL, Mcl-1, cyclin D1, cyclin D3, xenograft models, IM-9 cells
- MeSH terms
- Animals, Benzamides, Humans, Multiple Myeloma, Pyrazines, Signal Transduction, Apoptosis, Cell Line, Tumor, Cell Proliferation, STAT3 Transcription Factor, Mice, Tumor Microenvironment
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