LBH589 induces cytotoxicity in human MM cell lines resistant to conventional chemotherapy. (A) Viability of MM.1S, RPMI8226, U266, OPM1, and KMS11 at 48 hours was inhibited by LBH589 in a dose-dependent manner as demonstrated by MTS assay. (B) Growth of Dex-resistant MM.1R cells and RPMI8226 MM cells resistant to Dox (Dox40 cells), Mit (MR20 cells), or Mel (LR5 cells) was inhibited in a dose-dependent manner, as demonstrated by MTS assay. (C) Adhesion of MM.1S cells to BMSCs induced a significant increase in 3H-thymidine uptake by MM.1S cells at 48 hours, which was completely inhibited by LBH589. Supernatants from the experiment (C) were examined for cytokine secretion (D). LBH589 inhibited adhesion-induced up-regulation of IL-6 secretion in BMSCs triggered by coculture with MM.1S. (E) LBH589 up to 1 μM decreased BMSC viability, with 61% viability at 48 hours and 59% viability at 72 hours. Data represent mean ± SD of quadruplicate cultures.
