Fig. 1: Antitumor effects of EZH2 and G9a inhibition in MM.

A Effects of an EZH2 inhibitor (GSK126) and/or a G9a inhibitor (UNC0638) on MM cell viability. Shown are summarized cell viability assays in MM cell lines treated with the indicated drugs (1 μM each) for 3 or 6 days. Results are normalized to cells treated with DMSO. The data are presented as means of three biological replications; error bars represent standard errors of the mean (SEMs). B Western blot analysis of H3K9 and H3K27 methylation in RPMI-8226 cells treated with the indicated inhibitors (1 μM each, 6 days). C Tumor growth in mice injected with RPMI-8226 cells pretreated with DMSO or GSK126 + UNC0638 (1 μM each). Growth curves are presented as means of five biological replications. Resected tumors are shown below. D Results of cell viability assays using indicated MM cell lines treated with an EZH2 inhibitor (EPZ-6438, 1 μM) and/or a G9a inhibitor (UNC0642, 1 μM). Shown are means of three biological replications; error bars represent SEMs. E qRT-PCR analysis of EZH2 and EHMT2 in the indicated MM cell lines. Results are normalized to ACTB expression. Shown are means of three technical replications; error bars represent SEMs. F Results of cell viability assays of MM cell lines treated for 14 days with the indicated drugs (1 μM each). Shown are means of five biological replications; error bars represent SEMs. G Comparison of EZH2 mRNA expression among normal plasma cells (NPC, n = 15), newly diagnosed MM (NMM, n = 69) and relapsed MM (RMM, n = 28) (left), and EHMT2 mRNA expression among normal plasma cells (NPC, n = 22), monoclonal gammopathy of undetermined significance (MGUS, n = 44) and smoldering multiple myeloma (SmMM, n = 12) (right) using the indicated datasets. H Kaplan–Meier curves showing the effect of EZH2 or EHMT2 expression on overall survival of newly diagnosed MM patients from the indicated datasets. MST mean survival time, NR not reached. *P < 0.05, **P < 0.01.