A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Additive Benefits of Radium-223 Dichloride and Bortezomib Combination in a Systemic Multiple Myeloma Mouse Model
Tekijät: Suominen Mari I., Mäki-Jouppila Jenni, Huhtinen Anna, Sjöholm Birgitta, Rissanen Jukka P., Luostarinen Anniina, Fagerlund Katja M., Alhoniemi Esa, Siemeister Gerhard, Mumberg Dominik, Käkönen Sanna-Maria, Scholz Arne
Kustantaja: MDPI
Julkaisuvuosi: 2021
Journal: International Journal of Molecular Sciences
Tietokannassa oleva lehden nimi: International journal of molecular sciences
Lehden akronyymi: Int J Mol Sci
Artikkelin numero: 5570
Vuosikerta: 22
Numero: 11
ISSN: 1422-0067
eISSN: 1422-0067
DOI: https://doi.org/10.3390/ijms22115570
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.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
