The IL-6 receptor super-antagonist Sant7 enhances antiproliferative and apoptotic effects induced by dexamethasone and zoledronic acid on multiple myeloma cells.
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.
Tassone
Pierfrancesco
P
Oncology Unit, Department of Experimental and Clinical Medicine, University, I-88100 Catanzaro, Italy. tassone@unicz.it
Galea
Eulalia
E
Forciniti
Samantha
S
Tagliaferri
Pierosandro
P
Venuta
Salvatore
S
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
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