Effects of bortezomib on osteoclastogenesis in patients with multiple myeloma and their action mechanism / 肿瘤

ABSTRACT

Objective: To observe the effect of bortezomib (Btzmb) on the differentiation and function of osteoclasts from patients with multiple myeloma (MM) during their maturation in vitro and investigate the influence of Btzmb on the expression of tumor necrosis factor receptor-associated factor (TRAF6), one of the key signaling molecules on the upstream of osteoclasts differentiation. Methods: Osteoclast precursor mononuclear cells were isolated from peripheral blood of MM patients and cultured with receptor activator of NF-κB ligand (RANKL) and macrophage colony stimulating factor (M-CSF) and different concentrations of Btzmb. The number of tartrateresistan acid phosphatase (TRAP)-positive osteoclasts was counted. The TRAP activity in the supernatant was tested. The extent of the ivory slice resorption was observed. The effects of Btzmb on the mRNA and protein expressions of TRAF6 were determined by RT-PCR and Western blotting, respectively. Results: After Btzmb 2.5 and 5 nmol/L treatment, the number of osteoclasts were reduced compared with the control group [(157 ±21) and (98 ± 15) vs (307 ± 25), P < 0.05]. The number of the ivory slice resorption decreased [(53 ± 24)% and(29 ± 7)% of the control, P < 0.05]. The TRAP activity in the supernatant was inhibited [(86 ± 24)% and(60 ± 25)% of the control, P < 0.05]. The activity of TRAF6 protein gradually declined and the levels of TRAF6 mRNA also decreased at 24 h after Btzmb treatment. Conclusion: Btzmb can inhibite the differentiation and function of osteoclasts. The action of Btzmb may be related with TRAF6.