Zhang Yun-Kai, Dai Chunling, Yuan Chun-Gang, Wu Hsiang-Chun, Xiao Zhijie, Lei Zi-Ning, Yang Dong-Hua, Le X Chris, Fu Liwu, Chen Zhe-Sheng
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John׳s University, Queens, NY 11439, USA.
Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
Acta Pharm Sin B. 2017 Sep;7(5):564-570. doi: 10.1016/j.apsb.2017.04.001. Epub 2017 Apr 28.
Arsenic trioxide (ATO) is used as a chemotherapeutic agent for the treatment of acute promyelocytic leukemia. However, increasing drug resistance is reducing its efficacy. Therefore, a better understanding of ATO resistance mechanism is required. In this study, we established an ATO-resistant human epidermoid carcinoma cell line, KB/ATO, from its parental KB-3-1 cells. In addition to ATO, KB/ATO cells also exhibited cross-resistance to other anticancer drugs such as cisplatin, antimony potassium tartrate, and 6-mercaptopurine. The arsenic accumulation in KB/ATO cells was significantly lower than that in KB-3-1 cells. Further analysis indicated that neither application of P-glycoprotein inhibitor, breast cancer resistant protein (BCRP) inhibitor, or multidrug resistance protein 1 (MRP1) inhibitor could eliminate ATO resistance. We found that the expression level of ABCB6 was increased in KB/ATO cells. In conclusion, ABCB6 could be an important factor for ATO resistance in KB/ATO cells. The ABCB6 level may serve as a predictive biomarker for the effectiveness of ATO therapy.
三氧化二砷（ATO）用作治疗急性早幼粒细胞白血病的化疗药物。然而，不断增加的耐药性正在降低其疗效。因此，需要更好地了解ATO耐药机制。在本研究中，我们从其亲本KB-3-1细胞建立了一种耐ATO的人表皮样癌细胞系KB/ATO。除了ATO，KB/ATO细胞对其他抗癌药物如顺铂、酒石酸锑钾和6-巯基嘌呤也表现出交叉耐药性。KB/ATO细胞中的砷积累明显低于KB-3-1细胞。进一步分析表明，应用P-糖蛋白抑制剂、乳腺癌耐药蛋白（BCRP）抑制剂或多药耐药蛋白1（MRP1）抑制剂均不能消除ATO耐药性。我们发现ABCB6在KB/ATO细胞中的表达水平升高。总之，ABCB6可能是KB/ATO细胞中ATO耐药的一个重要因素。ABCB6水平可作为ATO治疗有效性的预测生物标志物。
Zotero 插件
