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Blood, Vol. 111, Issue 9, 4752-4763, May 1, 2008
Dual targeting of the proteasome regulates survival and homing in Waldenström macroglobulinemia
Blood Roccaro et al.
111: 4752
Supplemental materials for: Roccaro et al
Files in this Data Supplement:
- Figure S1. NPI-0052-induced cytotoxicity is enhanced in combination with bortezomib in tumor cells but not in normal PBMCs (JPG, 82.6 KB)
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Freshly isolated PBMCs from 3 healthy donors were cultured with NPI-0052 (2.5-80 nM), bortezomib (10 nM), or the combination NPI-0052 (10 nM) + bortezomib (10 nM) for 48 hours. Cytoxicity was assessed by MTT assay (Ai), and apoptosis by DNA fragmentation (Aii). (B) IgM secreting cell line (WM.WSU) were cultured with NPI-0052 (2.5, 5 and 10 nM for 48 hours, in the presence or absence of bortezomib (5 and 10 nM). Cytotoxicity was assessed by MTT assay. (C) Representative isobologram of NPI-0052 associated to bortezomib with the CalcuSyn software demonstrating synergy for the combination. (D) Combination indexes (C.I.) and fractions affected (FA) of the combinations of NPI-0052 and bortezomib. All experiments were repeated in triplicate. (E) BCWM.1 cells were cultured with either NPI-0052 (10 nM), bortezomib (10 nM), or the combination for 4 hours, in absence of TNF- . NF- Bp65 transcription factor-binding to its consensus sequence on the plate-bound oligonucleotide was studied from nuclear extracts. Wild type and mutant are wild type and mutated consensus competitor oligonucleotides, respectively. All results represent means (± sd) of triplicate experiments.
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