Activation of SHIP via a small molecule agonist kills multiple myeloma cells

摘要: Objective Multiple myeloma (MM) is a B-lymphocyte neoplasia that presently incurable because the tumor cells become resistant to currently available drugs. The growth and survival signals resulting from interactions between malignant clones bone marrow microenvironment are mediated chiefly through phosphoinositide 3′-kinase/Akt kinase signaling pathway. Thus agents can abrogate this pathway have great potential as targeted therapies. A novel approach in regard activation of Src homology 2-containing inositol 5′-phosphatase (SHIP), using small molecule agonist, AQX-MN100. Materials Methods SHIP agonist AQX-MN100 was tested vitro for its ability inhibit DNA synthesis, induce apoptosis MM cell lines, well phosphorylation kinases cascade. enhance cytotoxicity current therapeutic drugs dexamethasone bortezomib also examined. Results We demonstrate herein sufficient prevent while having no significant effects on nonhematopoietic lacking SHIP. augments established bortezomib. Conclusion These results provide basis further study activators improve patient outcomes.