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Anticancer Res. 2014 Sep;34(9):4767-73.

Expression of ABCB6 is related to resistance to 5-FU, SN-38 and vincristine.

Author information

1
Department of Molecular Oncology, Kagoshima University, Kagoshima, Japan Department of Clinical Pharmacy and Pharmacology, Kagoshima University, Kagoshima, Japan.
2
Department of Molecular Oncology, Kagoshima University, Kagoshima, Japan Department of Organic and Biological Chemistry, Graduate School of Science and Engineering, Kagoshima University, Kagoshima, Japan.
3
Department of Molecular Oncology, Kagoshima University, Kagoshima, Japan Institute for Advanced Biosciences, Keio University, Yamagata, Japan.
4
Department of Molecular Oncology, Kagoshima University, Kagoshima, Japan.
5
Department of Molecular Oncology, Kagoshima University, Kagoshima, Japan Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
6
College of Pharmacy and Allied Health Professions, Department of Pharmaceutical Sciences, St. John's University, Queens, NY, U.S.A.
7
Graduate School of Pharmaceutical Science, Osaka University, Osaka, Japan.
8
Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
9
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
10
Department of Molecular Oncology, Kagoshima University, Kagoshima, Japan Clinical Research Center, National Kyushu Cancer Center, Fukuoka, Japan.
11
Department of Organic and Biological Chemistry, Graduate School of Science and Engineering, Kagoshima University, Kagoshima, Japan.
12
Department of Clinical Pharmacy and Pharmacology, Kagoshima University, Kagoshima, Japan.
13
Department of Molecular Oncology, Kagoshima University, Kagoshima, Japan furukawa@m3.kufm.kogoshima-u.ac.jp.

Abstract

A previously established arsenite-resistant cell line, KAS, is also resistant to a variety of anticancer drugs. In order to understand responsible molecules for the multidrug resistance phenotype of KAS cells, we examined the expressions of ATP-binding cassette (ABC) transporters and found that the ABCB6 and ABCC1/ multidrug resistance protein 1 (ABCC1/MRP1) were increased. ABCC1/MRP1 was not completely responsible for the drug resistance spectrum of KAS cells and several reports have suggested that ABCB6 is related to anticancer drug and metal resistance. We, therefore, established and examined ABCB6-expressing KB cells and ABCB6-knockdown KAS cells. ABCB6 expression enhanced resistance to 5-fluorouracil (5-FU), SN-38 and vincristine (Vcr) but not to arsenite. Conversely, down-regulation of ABCB6 in KAS cells increased the sensitivity of KAS cells to 5-FU, SN-38 and Vcr, but not to arsenite. Our findings suggest that ABCB6 is involved in 5-FU, SN-38 and Vcr resistance.

KEYWORDS:

ABC transporters; ABCB6; anticancer agents; arsenite; drug resistance

PMID:
25202056
[Indexed for MEDLINE]

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