title: The IL-6 receptor super-antagonist Sant7 enhances antiproliferative and apoptotic effects induced by dexamethasone and zoledronic acid on multiple myeloma cells.
abstract: Interleukin-6 (IL-6) is the major growth and survival factor for multiple myeloma (MM), and has been shown to protect MM cells from apoptosis induced by a variety of agents. IL-6 receptor antagonists, which prevent the assembly of functional IL-6 receptor complexes, inhibit cell proliferation and induce apoptosis in MM cells. We have investigated whether the IL-6 receptor super-antagonist Sant7 might enhance the antiproliferative and apoptotic effects induced by the combination of dexamethasone (Dex) and zoledronic acid (Zln) on human MM cell lines and primary cells from MM patients. Here we show that each of these compounds individually induced detectable antiproliferative effects on MM cells. Sant7 significantly enhanced growth inhibition and apoptosis induced by Dex and Zln on both MM cell lines and primary MM cells. These results indicate that overcoming IL-6 mediated cell resistance by Sant7 potentiates the effect of glucocorticoides and bisphosphonates on MM cell growth and survival, providing a rationale for therapies including IL-6 antagonists in MM.
authors.affiliation: Oncology Unit, Department of Experimental and Clinical Medicine, University, I-88100 Catanzaro, Italy. tassone@unicz.it
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Tassone
authors.forename: Eulalia
authors.initials: E
authors.lastname: Galea
authors.forename: Samantha
authors.initials: S
authors.lastname: Forciniti
authors.forename: Pierosandro
authors.initials: P
authors.lastname: Tagliaferri
authors.forename: Salvatore
authors.initials: S
authors.lastname: Venuta
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D017209:Apoptosis; D002455:Cell Division / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D004164:Diphosphonates / Q000494:pharmacology*; D004357:Drug Synergism; D005434:Flow Cytometry; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D015850:Interleukin-6 / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D009101:Multiple Myeloma / Q000188:drug therapy*; D011509:Proteoglycans / Q000096:biosynthesis; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors*; D053667:Syndecans; D013997:Time Factors; D014407:Tumor Cells, Cultured; D000077211:Zoledronic Acid
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004164:Diphosphonates; D007093:Imidazoles; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D019947:Receptors, Interleukin-6; C432252:SANT-7; D053667:Syndecans; D000077211:Zoledronic Acid; D003907:Dexamethasone