PI-3K/Akt/GSK-3β signaling cascades stimulated by insulin like growth factor-I contribute to multiple myeloma cells proliferation and survival

摘要

Multiple myeloma is characterized by the accumulation of malignant plasma cells in the bone marrow. Significant progress in molecular mechanisms of signaling pathways underlying the survival and/or proliferation of these cells has been achieved. Interleukin 6 (IL-6) is an important cytokine leading to multiple myeloma (MM) cells growth and survival. However, some MM cells isolated from MM patients are poorly responsive to IL-6 stimulation or IL-6 independent. This phenomenon raises the possibility that other growth factors may also be involved in the development of MM. Insulin like growth factor-I (IGF-I) plays an important role in the proliferation of a variety of cell types, in the development and growth of multiple tumors and in the prevention of apoptosis. IGF-I has recently been reported to play such a role in stimulating the MM cells growth, it even induces MM cells proliferation in IL-6 dependent cells, yet the detailed signaling components triggered by IGF-I have not been completely clarified. Thus, the present study are to address the signaling cascades triggered by IGF-I in MM cells.