Multi-Drug–Resistant Cells Enriched From Chronic Myeloid Leukemia Cells by Doxorubicin Possess Tumor-Initiating–Cell Properties

Journal of Pharmacological Sciences

Ke Wang³  Xiaoran Qin³  Wenfu Tan²  Hong Xin²  Yizhun Zhu²  Ying Kong²  Ze-Hong Miao⁴  Xiaoxiao Jiang¹ 

[1] Department of Pharmacology, Shandong University at Weihai, China;Department of Pharmacology, School of Pharmacy, Fudan University, China;Department of Pharmacology, Shanghai ChemPartner Co., Ltd., China;State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China

关键词: multi-drug resistance;    K562/A02;    tumor-initiating cell;    snail;    twist1;   

DOI  :  10.1254/jphs.13025FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(19)Cited-By(7)Multiple drug resistance (MDR) occurring during chemotherapy is a major obstacle for treatment of cancers using chemotherapeutic drugs; thus, the mechanisms underlying MDR have attracted intensive attention. Many studies have shown that tumor-initiating cells exhibit a chemotherapeutic tolerance characteristic. However, whether the MDR cells possess tumor-initiating cells properties and its underlying mechanisms remain to be fully elucidated. In this study, we utilized a well-established MDR cell line K562/A02 enriched by doxorubicin from K562 cells to determine if the K562/A02 cells possess tumor-initiating properties and investigated its potential molecular mechanisms. We observed that the expressions of Oct4, Sox2, and Nanog, all of which are well-characterized stem cell markers, in K562/A02 cells were elevated in comparison to parental K562 cells; in addition, we found that K562/A02 cells exhibited more potent in vitro and in vivo tumor-initiating properties, as revealed by sphere assay, self-renewal assay, soft agar assay, and animal studies. Furthermore, our data suggest that snail and twist1, two well known transcriptional factors for the epithelial-mesenchymal transition (EMT) program, may be potentially involved in the acquisition of tumor-initiating properties of K562/A02 cells. Thus, our study demonstrates that MDR K562/A02 cells possess tumor-initiating properties, most likely due to the elevated expressions of snail and twist1.

【 授权许可】

Unknown