Abstract
Bortezomib is commonly used in treating multiple myeloma (MM). However, a number of patients develop resistance to bortezomib over time. Cox-2 is overexpressed in MMcells and contributes to apoptosis resistance and MM development. In the present study, RPMI8226 MM cells were treated with the Cox-2 inhibitor NS-398 to investigate whether it enhanced the effect of bortezomib on MM. The results showed that NS-398 and bortezomib acted synergistically to inhibit growth, arrest the cell cycle at the G1phase and to induce the apoptosis of MM cells. NS-398 inhibited the NF-κB p65 protein levels and the expression of various NF-κB target genes, including cyclinD1, c-Myc, survivin and Bcl-2. In conclusion, NS-398 enhanced the efficacy of bortezomib against MM cells invitro and this was associated with the inhibition of NF-κB signaling. These findings suggest that the combined use of NS-398 and bortezomib may constitute a promising novel treatment protocol for MM patients.
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