TY - JOUR T1 - Synergistic Cytotoxicity of Bendamustine and the BTK Inhibitor in a Mantle Cell Lymphoma Cell Line JF - Anticancer Research JO - Anticancer Res SP - 6679 LP - 6684 VL - 35 IS - 12 AU - KAZUMI HAGIWARA AU - TAKASHI TOKUNAGA AU - HIROATSU IIDA AU - HIROKAZU NAGAI Y1 - 2015/12/01 UR - http://ar.iiarjournals.org/content/35/12/6679.abstract N2 - Background: Bendamustine is effective in B-cell malignancies, including mantle cell lymphoma (MCL), alone and in combination with other agents. This study investigated the combination effect of bendamustine and the Bruton tyrosine kinase (BTK) inhibitor PCI-32765 on MCL cell death and the underlying mechanisms. Materials and Methods: Cytotoxicity was examined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MIT) assay. Apoptosis was assessed by annexin V/propidium iodide staining and protein expression was analyzed by western blotting. Results: When combined with bendamustine, PCI-32765 showed a synergistic effect on growth inhibition of the MCL cell line Jeko-1. Cleavage of caspase-3 and poly-(ADP-ribose) polymerase was increased, indicating enhanced apoptosis induction. In addition, this combination decreased the protein expression of cyclin D1. Phosphorylated v-akt murine thymoma viral oncogene homolog 1 (AKT) (Ser473) was also down-regulated, suggesting a suppression of the phosphatidylinositol 3-kinase/AKT signaling pathway. Conclusion: Combination treatment with bendamustine and a BTK inhibitor may be effective in MCL therapy. ER -