title: Expression of ABCB6 is related to resistance to 5-FU, SN-38 and vincristine.
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.
authors.affiliation: Department of Molecular Oncology, Kagoshima University, Kagoshima, Japan Department of Clinical Pharmacy and Pharmacology, Kagoshima University, Kagoshima, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Minami
authors.affiliation: Department of Molecular Oncology, Kagoshima University, Kagoshima, Japan Department of Organic and Biological Chemistry, Graduate School of Science and Engineering, Kagoshima University, Kagoshima, Japan.
authors.forename: Youhei
authors.initials: Y
authors.lastname: Kamijo
authors.affiliation: Department of Molecular Oncology, Kagoshima University, Kagoshima, Japan Department of Clinical Pharmacy and Pharmacology, Kagoshima University, Kagoshima, Japan.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Nishizawa
authors.affiliation: Department of Molecular Oncology, Kagoshima University, Kagoshima, Japan Institute for Advanced Biosciences, Keio University, Yamagata, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Tabata
authors.affiliation: Department of Molecular Oncology, Kagoshima University, Kagoshima, Japan Department of Organic and Biological Chemistry, Graduate School of Science and Engineering, Kagoshima University, Kagoshima, Japan.
authors.forename: Fumito
authors.initials: F
authors.lastname: Horikuchi
authors.affiliation: Department of Molecular Oncology, Kagoshima University, Kagoshima, Japan.
authors.forename: Masatatsu
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Department of Molecular Oncology, Kagoshima University, Kagoshima, Japan.
authors.forename: Kohich
authors.initials: K
authors.lastname: Kawahara
authors.affiliation: Department of Molecular Oncology, Kagoshima University, Kagoshima, Japan.
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Shinsato
authors.affiliation: Department of Molecular Oncology, Kagoshima University, Kagoshima, Japan Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Tokushi
authors.initials: T
authors.lastname: Tachiwada
authors.affiliation: College of Pharmacy and Allied Health Professions, Department of Pharmaceutical Sciences, St. John's University, Queens, NY, U.S.A.
authors.forename: Zhe-Sheng
authors.initials: ZS
authors.lastname: Chen
authors.affiliation: Graduate School of Pharmaceutical Science, Osaka University, Osaka, Japan.
authors.forename: Kazutake
authors.initials: K
authors.lastname: Tsujikawa
authors.affiliation: Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakagawa
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Seki
authors.affiliation: Department of Molecular Oncology, Kagoshima University, Kagoshima, Japan Clinical Research Center, National Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Akiyama
authors.affiliation: Department of Organic and Biological Chemistry, Graduate School of Science and Engineering, Kagoshima University, Kagoshima, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Arima
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, Kagoshima University, Kagoshima, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takeda
authors.affiliation: Department of Molecular Oncology, Kagoshima University, Kagoshima, Japan furukawa@m3.kufm.kogoshima-u.ac.jp.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Furukawa
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005472:Fluorouracil / Q000494:pharmacology*; D015870:Gene Expression; D006801:Humans; D000077146:Irinotecan; D007624:KB Cells; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014750:Vincristine / Q000494:pharmacology*
chemical_list: D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D002166:Camptothecin; D005472:Fluorouracil; D000077146:Irinotecan; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D014750:Vincristine; C107991:ABCB6 protein, human; C421109:multidrug resistance-associated protein 1
keywords: ABC transporters; ABCB6; anticancer agents; arsenite; drug resistance