title: NS-398 enhances the efficacy of bortezomib against RPMI8226 human multiple myeloma cells.
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 MM cells 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 G1 phase 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 cyclin D1, c-Myc, survivin and Bcl-2. In conclusion, NS-398 enhanced the efficacy of bortezomib against MM cells in vitro 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.
authors.affiliation: Department of Hematology and Rheumatology, The Third Affiliated Hospital of Fujian Medical University, Fuzhou 350003, PR China.
authors.forename: Wenzhong
authors.initials: W
authors.lastname: Que
authors.forename: Saiyuan
authors.initials: S
authors.lastname: Li
authors.forename: Junmin
authors.initials: J
authors.lastname: Chen
mesh_terms: D017209:Apoptosis; D001897:Boronic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D000069286:Bortezomib; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D009578:Nitrobenzenes / Q000494:pharmacology / Q000627:therapeutic use*; D011719:Pyrazines / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D001897:Boronic Acids; D016328:NF-kappa B; D009578:Nitrobenzenes; D011719:Pyrazines; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D000069286:Bortezomib; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human