PT  - JOURNAL ARTICLE
AU  - KAZUMI HAGIWARA
AU  - TAKASHI TOKUNAGA
AU  - HIROATSU IIDA
AU  - HIROKAZU NAGAI
TI  - Synergistic Cytotoxicity of Bendamustine and the BTK Inhibitor in a Mantle Cell Lymphoma Cell Line
DP  - 2015 Dec 01
TA  - Anticancer Research
PG  - 6679--6684
VI  - 35
IP  - 12
4099  - http://ar.iiarjournals.org/content/35/12/6679.short
4100  - http://ar.iiarjournals.org/content/35/12/6679.full
SO  - Anticancer Res2015 Dec 01; 35
AB  - 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.