Additive Benefits of Radium-223 Dichloride and Bortezomib Combination in a Systemic Multiple Myeloma Mouse Model
| Autor: | Dominik Mumberg, Anniina Luostarinen, Mari I. Suominen, Jenni H. Mäki-Jouppila, Katja M. Fagerlund, Birgitta Sjöholm, Jukka P. Rissanen, Sanna-Maria Käkönen, Gerhard Siemeister, Arne Scholz, Anna Huhtinen, Esa Alhoniemi |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
targeted alpha-therapy Bone disease radium-223 Mice 0302 clinical medicine Antineoplastic Combined Chemotherapy Protocols Bone cell Biology (General) Spectroscopy Multiple myeloma myeloma bone disease Bortezomib bortezomib Bone metastasis Osteoblast General Medicine Computer Science Applications multiple myeloma Chemistry medicine.anatomical_structure 030220 oncology & carcinogenesis osteoclast osteoblast systemic model Radium medicine.drug Combination therapy QH301-705.5 dexamethasone 5TGM1 mouse model Article Catalysis Inorganic Chemistry 03 medical and health sciences Cell Line Tumor medicine Animals Humans Physical and Theoretical Chemistry Molecular Biology QD1-999 Radioisotopes business.industry Organic Chemistry Neoplasms Experimental medicine.disease 030104 developmental biology Proteasome inhibitor Cancer research business |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 5570, p 5570 (2021) International Journal of Molecular Sciences Volume 22 Issue 11 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | Osteolytic bone disease is a hallmark of multiple myeloma (MM) mediated by MM cell proliferation, increased osteoclast activity, and suppressed osteoblast function. The proteasome inhibitor bortezomib targets MM cells and improves bone health in MM patients. Radium-223 dichloride (radium-223), the first targeted alpha therapy approved, specifically targets bone metastases, where it disrupts the activity of both tumor cells and tumor-supporting bone cells in mouse models of breast and prostate cancer bone metastasis. We hypothesized that radium-223 and bortezomib combination treatment would have additive effects on MM. In vitro experiments revealed that the combination treatment inhibited MM cell proliferation and demonstrated additive efficacy. In the systemic, syngeneic 5TGM1 mouse MM model, both bortezomib and radium-223 decreased the osteolytic lesion area, and their combination was more effective than either monotherapy alone. Bortezomib decreased the number of osteoclasts at the tumor–bone interface, and the combination therapy resulted in almost complete eradication of osteoclasts. Furthermore, the combination therapy improved the incorporation of radium-223 into MM-bearing bone. Importantly, the combination therapy decreased tumor burden and restored body weights in MM mice. These results suggest that the combination of radium-223 with bortezomib could constitute a novel, effective therapy for MM and, in particular, myeloma bone disease. |
| Databáze: | OpenAIRE |
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