Antitumor activity and drug interactions of proteasome inhibitor Bortezomib in human high-risk myelodysplastic syndrome cells
作者： Jian Huang , Ting Ding , Min Yang , Hui Liu , Xin Sun
DOI: 10.1007/S12185-011-0821-Z
关键词:
摘要: The purpose of this study was to investigate the antitumor effects and drug interactions proteasome inhibitor Bortezomib against high-risk myelodysplastic syndrome (MDS) cells in vitro vivo. MDS-derived MUTZ-1 cell line bone marrow mononuclear from primary MDS patients were used examine activity for Bortezomib. Apoptotic proteins, including caspase Bcl-2 family members, as well protein FLIP, studied. Phosphoinositide 3-kinase (PI3K)/Akt MAPK signaling pathways also examined. PI3K LY294002 involvement PI3K/Akt pathway induction apoptosis. Cytarabine (AraC) daunorubicin (DNR) test synergistic between chemotherapeutic agents. SCID mice xenografted with vivo study. We found that could induce growth arrest apoptosis mechanisms related decreased activation survival pathway, but not involved inhibition NF-κB downregulation Bcl-2/Bax FLIPL/FLIPS ratios, triggering cascades. This phenomenon inhibited by LY294002. acted synergistically agents AraC DNR, which are associated activity. Our results demonstrate can had a effect two findings provide new insights treatment MDS, using either alone, or combination conventional antineoplastic
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