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V.G. Ramakrishnan et al.
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Figure 1. MEK inhibition in combination with histone deacetylase inhibition synergistically kills multiple myeloma cell lines in vitro. (A) AZD6244 and the pan-histone deacetylase (HDAC) inhibitor LBH589 induced synergistic cytotoxicity, assayed using MTT at 72 h in the RAS-mutated human multiple myeloma (MM) cell lines H929, MM1S, and RPMI8226, and the RAF-mutated human MM cell line U266. Viability is shown as percent of control on the Y-axis. Combination index (CI) values <1.0, indicating synergy, are shown for each cell line. (B) AZD6244 and LBH589 induced proliferation arrest, assayed with 3H-thymidine incorporation, by 48 h in H929, MM1S, RPMI8226, and U266 cells, shown as percent of control on the Y-axis. (C) Bone marrow stromal cells (BMSC) derived from an MM patient were co-cultured with MM1S, and proliferation was assayed using 3H-thymidine incorporation after treatment for 48 h with AZD6244, LBH5589, or the combination. Error bars represent the standard error of the mean of triplicate experiments. Differences between groups were calculated with the Student t test. **P<0.001, ##P<0.01. All experiments were performed in triplicate.
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haematologica | 2019; 104(10)
