XIAP is upregulated in HL-60 cells cocultured with stromal cells by direct cell contact

✍ Scribed by Xiaofang Wang; Chun Wang; Shi-Ke Yan; Yan-Rong Gao

• Book ID: 104040272
• Publisher: Elsevier Science
• Year: 2007
• Tongue: English
• Weight: 291 KB
• Volume: 31
• Category: Article
• ISSN: 0145-2126
• DOI: 10.1016/j.leukres.2006.09.006

✦ Synopsis

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.