Department of Molecular Oncology, Kagoshima University, Kagoshima, Japan Department of Clinical Pharmacy and Pharmacology, Kagoshima University, Kagoshima, Japan.
Department of Molecular Oncology, Kagoshima University, Kagoshima, Japan Department of Organic and Biological Chemistry, Graduate School of Science and Engineering, Kagoshima University, Kagoshima, Japan.
Anticancer Res. 2014 Sep;34(9):4767-73.
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.
先前建立的亚砷酸盐抗性细胞系 KAS 也对多种抗癌药物具有抗性。为了了解 KAS 细胞多药耐药表型的负责分子，我们检查了 ATP 结合盒（ABC）转运蛋白的表达情况，发现 ABCB6 和 ABCC1/多药耐药蛋白 1（ABCC1/MRP1）增加。ABCC1/MRP1 并不是 KAS 细胞耐药谱的完全负责因素，有几项报告表明 ABCB6 与抗癌药物和金属耐药有关。因此，我们建立并检查了表达 ABCB6 的 KB 细胞和 ABCB6 敲低的 KAS 细胞。ABCB6 的表达增强了对 5-氟尿嘧啶（5-FU）、SN-38 和长春新碱（Vcr）的耐药性，但对亚砷酸盐没有。相反，KAS 细胞中 ABCB6 的下调增加了 KAS 细胞对 5-FU、SN-38 和 Vcr 的敏感性，但对亚砷酸盐没有。我们的研究结果表明，ABCB6 参与了 5-FU、SN-38 和 Vcr 的耐药性。
