白血病K562/ADM细胞耐药性与白血病干细胞及耐药蛋白表达的关系 |
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引用本文: | 易娟,陈静,孙静,魏虎来. 白血病K562/ADM细胞耐药性与白血病干细胞及耐药蛋白表达的关系[J]. 中华医学杂志, 2003, 89(1): 1741-1744. DOI: 10.3760/cma.j.issn.0376-2491.2009.25.006 |
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作者姓名: | 易娟 陈静 孙静 魏虎来 |
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作者单位: | 甘肃省新药临床前研究重点实验室,兰州大学基础医学院医学实验中心,730000; |
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基金项目: | 中草药物质基础与资源利用教育部重点实验室(北京协和医学院)开放课题资助项目甘肃省新药临床前研究重点实验室(兰州大学)开放课题资助项目 |
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摘 要: | Objective To investigate the drug resistance, proportion of leukemia stem cells (LSC) and expression of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) in drug-sensitive and multidrug-resistant leukemia cell population. Methods The multidrug-resistant leukemia K562/ADM cell and its parental K562 cell were used as the model cells. The drug sensitivity was tested with a MTI" assay. Flow cytometry was employed to detect the immunophenotype of stem celia and the expression of P-gp and BCRP. The serf-renewal and proliferating potential were examined with methylcellulose colony-formlng unit assay. Results K562/ADM cells were highly resistant to adriamycin, daunorubincin and etoposide. The amount of CD34+, CD123+ and CD34+ CD38- cells in K562/ADM cells was much higher than that in K562 cells, and the proportion of CD34+ CD38-CD123+ cells(LSC) in K562/ADM cells was (5.23 ± 0. 21) % versus (1.27 ± 0. 17) % in K562 cells, which was 4. 12-fold higher than that in K562 cells. Both P-gp and BCRP were overexpressed in K562/ADM cells relative to K562 cells, and the K562/ADM cells co-expressing P-gp and BCRP were 11.25-fold higher over K562 cells. The proportion of CD34+ CD38- CD123+BCRP+ and CD34+ CD38- P-gp+ BCRP+cells in K562/ADM cells were (4. 13±0.40)% and (5. 80 ± 1.19)% respectively, which were 3.66- and 11. 37-fold higher than the same cells in K562 cells [(1.13 ± 0. 15) % and (0. 51 ± 0. 01) %]. Furthermore, drug-resistant K562/ADM cells displayed 4. 17-time greater colony-forming ability over the parent K562 cells, corresponding to the proportion of LSCs in K562/ADM cells. Conclusions The ABC transporters-overexpressing LSC population exists in drug-resistant leukemic K562/ADM cells relative to drug-sensitive K562 cells, and the drug-resistant LSCs may be the source of chemotherapeutic resistance of leukemia.
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关 键 词: | 抗药性,多药 P-糖蛋白 乳腺癌耐药蛋白 集落形成 白血病干细胞 |
The relationship between multi-drug resistance and proportion of leukemia stem cells and expression of drug transporters in drug-resistant leukemia K562/ADM cells |
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Abstract: | |
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Keywords: | Drug resistance multipleP-glycoproteinBCRP protein humanColony-forming units assayLeukemia stem cell |
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