Synergistic effect of bortezomib and valproic acid treatment on the proliferation and apoptosis of acute myeloid leukemia and myelodysplastic syndrome cells
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Ai-Hua Wang & Lin Wei & Li Chen & Shu-Qing Zhao & Wei-Li Wu & Zhi-Xiang Shen & Jun-Min Li
- چاپ و سال / کشور: 2011
Description
The synergistic effect of proteasome inhibitor bortezomib and valproic acid (VPA), a histone deacetylase inhibitor, were investigated in this study. Co-treatment with VPA and bortezomib on acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) cell lines resulted in marked inhibition of proliferation and induction of apoptosis, including a striking increase in mitochondrial injury, caspase cascade activation, and altered expression of Bcl-2 family proteins. Moreover, combination treatment inhibited cyto-protective signaling pathways, including inactivation of nuclear factor κB (NF-κB), the extracellular signalrelated kinase (ERK) and Akt pathways, and activated stress-related signaling pathway, including the c-jun Nterminal kinase (JNK) and p38 mitogen-activated protein kinase (p38) pathways. In addition, this regimen significantly caused G2/M phase arrest, while downregulating the expression of phospho-CDC2 and CyclinD1 as well as increasing p21cip1. Furthermore, combination treatment efficiently induced apoptosis in primary AML/MDS cells, with little effect on normal cells. In summary, these findings indicate that combination treatment with VPA and bortezomib may be a potent therapy for AML/MDS malignancies.
Ann Hematol (2011) 90:917–931 DOI 10.1007/s00277-011-1175-6 Received: 19 February 2010 / Accepted: 27 January 2011 / Published online: 22 February 2011
