XIAP is upregulated in HL-60 cells cocultured with stromal cells by direct cell contact.
Apoptosis resistance is an important mechanisms of drug resistance mediated by bone marrow stromal cells (BMSCs). BMSCs influence tumor cells survival through several mechanisms including direct cell-cell contact and the effects of soluble factors. In this research we investigated the role of X-linked inhibitor of apoptosis protein (XIAP) in the apoptosis resistance mediated by stromal cells in HL-60 cells and the signaling pathway involved. We found that bone marrow stromal-derived soluble factors and direct cell contact both prevented apoptosis of HL-60 cells. XIAP is upregulated by direct cell contact but not by soluble factors. Phosphatidylinositol 3-kinase (PI3K) and Akt were activated and LY294002 downregulated XIAP and increased apoptosis in HL-60 cells co-cultured with BMSCs. The results indicated that PI3K/Akt/XIAP is an important pathway involved in the apoptosis resistance of HL-60 cells co-cultured with BMSCs by direct cell contact. Inhibition of this signaling pathway may provide a new therapeutic strategy for acute myeloid leukemia treatment.
Wang
Xiaofang
X
Department of Hematology, Cancer Hospital of Tianjin, Tianjin Medical University, Ti-Yuan-Bei, Huan-Hu-Xi Road, Tianjin, PR China. xiaofangwang2005@163.com
Wang
Chun
C
Yan
Shi-Ke
SK
Gao
Yan-Rong
YR
D017209:Apoptosis; D015153:Blotting, Western; D001853:Bone Marrow / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D002450:Cell Communication; D002867:Chromones / Q000494:pharmacology; D018920:Coculture Techniques; D018922:HL-60 Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism*
D002867:Chromones; D009025:Morpholines; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt