Establishment and characterization of arsenic trioxide resistant KB/ATO cells.
10.1016/j.apsb.2017.04.001
- Author:
Yun-Kai ZHANG
1
;
Chunling DAI
1
;
Chun-Gang YUAN
2
;
Hsiang-Chun WU
1
;
Zhijie XIAO
1
;
Zi-Ning LEI
1
;
Dong-Hua YANG
1
;
X Chris LE
2
;
Liwu FU
3
;
Zhe-Sheng CHEN
1
Author Information
1. Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John׳s University, Queens, NY 11439, USA.
2. Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton T6G 2G3, Alberta, Canada.
3. 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.
- Publication Type:Journal Article
- Keywords:
ABCB6;
Arsenic trioxide;
Biomarker;
KB-3-1 cells;
KB/ATO cells;
Multidrug resistance
- From:
Acta Pharmaceutica Sinica B
2017;7(5):564-570
- CountryChina
- Language:English
-
Abstract:
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.
