title: XIAP is upregulated in HL-60 cells cocultured with stromal cells by direct cell contact.
abstract: 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.
authors.affiliation: Department of Hematology, Cancer Hospital of Tianjin, Tianjin Medical University, Ti-Yuan-Bei, Huan-Hu-Xi Road, Tianjin, PR China. xiaofangwang2005@163.com
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Wang
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
authors.forename: Shi-Ke
authors.initials: SK
authors.lastname: Yan
authors.forename: Yan-Rong
authors.initials: YR
authors.lastname: Gao
mesh_terms: 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*
chemical_list: 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