The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells.

摘要: Human multiple myeloma (MM) is a presently incurable hematological malignancy, and novel biologically based therapies are urgently needed. Proteasome inhibitors represent potential anticancer therapy. In this study, we demonstrate that the proteasome inhibitor PS-341 directly inhibits proliferation induces apoptosis of human MM cell lines freshly isolated patient cells; mitogen-activated protein kinase growth signaling in despite induction p21 p27 both p53 wild-type mutant overcomes drug resistance; adds to anti-MM activity dexamethasone; resistance cells conferred by interleukin-6. also paracrine decreasing their adherence bone marrow stromal (BMSCs) related nuclear factor kappaB-dependent interleukin-6 secretion BMSCs, as well inhibiting residual adherent cells. These data, therefore, acts on alters cellular interactions cytokine BM millieu inhibit tumor growth, induce apoptosis, overcome resistance. Given acceptable animal toxicity profile PS-341, these studies provide framework for clinical evaluation improve outcome patients with universally fatal malignancy.