engleski

Effect of BMP-2 and bortezomib on four multiple myeloma cell lines

Background. Multiple myeloma (MM) is a B-cell malignancy characterized by the proliferation of plasma cells in the bone marrow. Apoptosis of MM cells can be induced by bortezomib and, possibly, by the bone morphogenetic proteins (BMPs), which are abundant within the bone marrow. The aim of our study was to test the interaction of bortezomib with BMP-2, using four MM cell lines. Methods. JJN-3, NCI-H929, RPMI-8226, and Thiel cell lines were treated with different concentrations of bortezomib (1-1000 nmol/mL) for 24, 48, and 72 hours ; BMP-2 (2-5000 ng/mL) for 72 hours ; or the combination of both drugs for 72 hours. Cell proliferation was assessed using MTT colorimetric assay, whereas cell viability and apoptosis were assessed by Annexin V-FITC/Propidium iodide staining and flow cytometry. Results. Different cell lines showed great differences in the sensitivity to BMP-2- and bortezomid-induced increase in the cell death and apoptosis. The treatment with BMP-2 caused the decrease in cell proliferation and viability in a dose dependent manner, causing the most prominent effect in NCI and Thiel cell lines (approximately 3 fold increase in the percent of the death cells for both lines after the treatment with 5000 ng/mL of BMP-2). Bortezomib was able to inhibit cell proliferation as well as to increase the percent of death and apoptotic cell in all used cell lines, again with the most prominent effect in NCI and Thiel cells (5-6 fold increase in the percent of the death and apoptotic cells for both lines after the treatment with 8 nmol/mL of bortezomib). The combined treatment with both BMP-2 and bortezomib showed some additive effect on cell proliferation and viability. Conclusions. Our results showed that both BMP-2 and bortezomib do affect MM cell survival in a dose dependent manner. Different MM cell lines were not equally sensitive to the treatment, with the greatest sensitivity of NCI and Thiel cell lines. Also, we achieved some additive effect with the combined treatment. Drug combinations are always desirable, due to the possibility to affect tumor cells by different mechanisms of action. Therefore, our preliminary results of the possible additive effects are promising and need to be further investigated.

multiple myeloma; BMP-2; bortezomib; apoptosis

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