期刊
JOURNAL OF PHARMACOLOGICAL SCIENCES
卷 122, 期 4, 页码 299-304出版社
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1254/jphs.13025FP
关键词
multi-drug resistance; K562/A02; tumor-initiating cell; snail; twist1
资金
- National Natural Science Foundation of China [81173077]
- Interdisciplinary Cooperation Team Program for Science and Technology Innovation of the Chinese Academy of Sciences
- State Key Laboratory of Drug Research of Chinese Academy of Sciences [SIMM1004KF-07]
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 twist 1, 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
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