Publication Date:
2014-12-06
Description:
Background: We investigated the potency, biological mechanisms of action, and described the role of MYC in cell death to the proteasome inhibitor, ixazomib (MLN2238), in TCL and HL in vitro and in vivo tumor models. In addition, we sought to identify molecular biomarkers that were associated with response/resistance to ixazomib. Methods: TCL cell lines (Jurkat, Hut78, HH) and HL cell lines (L428, L540, L1236) were treated with ixazomib for 24-72 hours, cell viability and apoptosis were analyzed by MTT and Annexin/PI by flow cytometry (FC). In vivo anti-tumor activity and survival of tumor bearing SCID mice were determined using xenografts derived from Jurkat (TCL) and L540 (HL) cell lines. Gene expression profiling (GEP) was performed using Human Affymetrix 2.0 HT array, which included Gene Set Enrichment Analysis (GSEA), for Jurkat, L540, and L428 cell lines. Results: Treatment with 20-100 nanomolar (nM) of ixazomib resulted in time- and dose-dependent cytotoxicity and apoptosis in all TCL and HL cell lines with all IC50’s
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine