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Establishment and Characteristics of a Novel Mantle Cell Lymphoma-derived Cell Line and a Bendamustine-resistant Subline.
Takimoto-Shimomura, Tomoko; Nagoshi, Hisao; Maegawa, Saori; Fujibayashi, Yuto; Tsukamoto, Taku; Matsumura-Kimoto, Yayoi; Mizuno, Yoshimi; Chinen, Yoshiaki; Mizutani, Shinsuke; Shimura, Yuji; Horiike, Shigeo; Taniwaki, Masafumi; Kobayashi, Tsutomu; Kuroda, Junya.
Affiliation
  • Takimoto-Shimomura T; Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
  • Nagoshi H; Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
  • Maegawa S; Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
  • Fujibayashi Y; Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
  • Tsukamoto T; Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
  • Matsumura-Kimoto Y; Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
  • Mizuno Y; Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
  • Chinen Y; Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
  • Mizutani S; Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
  • Shimura Y; Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
  • Horiike S; The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
  • Taniwaki M; Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
  • Kobayashi T; Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
  • Kuroda J; Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Cancer Genomics Proteomics ; 15(3): 213-223, 2018.
Article in En | MEDLINE | ID: mdl-29695404
ABSTRACT
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Gene Expression Regulation, Neoplastic / Drug Resistance, Neoplasm / Cell Culture Techniques / Lymphoma, Mantle-Cell / Bendamustine Hydrochloride Limits: Humans / Male / Middle aged Language: En Journal: Cancer Genomics Proteomics Journal subject: BIOQUIMICA / GENETICA MEDICA / NEOPLASIAS Year: 2018 Document type: Article Affiliation country: Japan
Fulltext
Add to My VHL
Print
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Gene Expression Regulation, Neoplastic / Drug Resistance, Neoplasm / Cell Culture Techniques / Lymphoma, Mantle-Cell / Bendamustine Hydrochloride Limits: Humans / Male / Middle aged Language: En Journal: Cancer Genomics Proteomics Journal subject: BIOQUIMICA / GENETICA MEDICA / NEOPLASIAS Year: 2018 Document type: Article Affiliation country: Japan