TY - JOUR T1 - Establishment and Characteristics of a Novel Mantle Cell Lymphoma-derived Cell Line and a Bendamustine-resistant Subline JF - Cancer Genomics - Proteomics JO - Cancer Genomics Proteomics SP - 213 LP - 223 VL - 15 IS - 3 AU - TOMOKO TAKIMOTO-SHIMOMURA AU - HISAO NAGOSHI AU - SAORI MAEGAWA AU - YUTO FUJIBAYASHI AU - TAKU TSUKAMOTO AU - YAYOI MATSUMURA-KIMOTO AU - YOSHIMI MIZUNO AU - YOSHIAKI CHINEN AU - SHINSUKE MIZUTANI AU - YUJI SHIMURA AU - SHIGEO HORIIKE AU - MASAFUMI TANIWAKI AU - TSUTOMU KOBAYASHI AU - JUNYA KURODA Y1 - 2018/05/01 UR - http://cgp.iiarjournals.org/content/15/3/213.abstract N2 - Background/Aim: Bendamustine hydrochloride (BH) is a key therapeutic agent for mantle cell lymphoma (MCL), while the mechanism underlying BH-resistance has not been verified. Materials and Methods: We compared molecular/biological characteristics of a newly-generated MCL-derived cell line KPUM-YY1 and its BH-resistant subline KPUM-YY1R. Results: The growth-inhibitory IC50 for BH was 20 μM in KPUM-YY1 cells, while cell proliferation was not inhibited by up to 60 μM BH in KPUM-YY1R cells. Compared to KPUM-YY1 cells, gene expression profiling in KPUM-YY1R cells revealed up-regulation of 312 genes, including ABCB1 encoding P-glycoprotein (P-gp), and microsomal glutathione S-transferase 1 (MGST1). Addition of either a P-gp inhibitor or a GST inhibitor, at least partly, restored sensitivity to BH in KPUM-YY1R cells. In addition, KPUM-YY1R cells showed cross-resistance against various anti-MCL chemotherapeutics. Conclusion: BH resistance is mediated by overlapping mechanisms with overexpression of ABCB1 and MGST1, and is potentially accompanied by multidrug resistance in MCL. ER -