白血病K562/ADM耐药细胞中白血病干细胞及其耐药蛋白的表达
首发时间:2008-09-23
摘要:目的:比较观察白血病药物敏感和耐受细胞中白血病干细胞(leukemia stem cell, LSC)及其生物学特性。方法:以白血病多药耐药株K562/ADM细胞及其药物敏感的亲本K562细胞为模型,采用流式细胞术检测干细胞免疫标志,以及耐药蛋白P-糖蛋白(P-glycoprotein, P-gp)和乳腺癌耐药蛋白(breast cancer resistance protein,BCRP)的表达;甲基纤维素集落形成法检测细胞的自我更新和增殖能力。结果:K562/ADM细胞中CD34+、CD123+和CD34+CD38-细胞含量均显著高于K562细胞,CD34+CD38-CD123+(LSC)细胞含量是K562细胞的4倍;K562/ADM细胞高表达P-gp和BCRP,其中CD34+细胞和CD123+细胞表达BCRP1者显著高于K562细胞;约4%的K562/ADM细胞共表达P-gp和BCRP,其比例与其LSC含量接近;K562/ADM细胞集落形成能力较K562细胞为强,K562/ADM细胞集落形成率是K562细胞的4倍。结论:白血病耐药细胞群中存在较高含量的LSC,耐药性LSC是白血病治疗抗性的根源。
关键词: 白血病干细胞 多药耐药性 P-糖蛋白 乳腺癌耐药蛋白 集落形成
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The leukemia stem cells and expression of multidrug transporters in multi-drug resistant leukemia K562/ADM cells
Abstract:OBJECTIVE: To compare the content of leukemia stem cells and expression of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) in drug-sensitive and multidrug-resistant leukemia cells. METHODS: The multidrug-resistant leukemia K562/ADM cell and its parental K562 cell were used as the model cells. Flow cytometry was employed to detect the immunophenotypis of stem cells and the expression of P-gp and BCRP. The self-renewal and proliferating activity were examined with colony-forming assay. RESULTS: The amount of CD34+、CD123+ and CD34+CD38- cells in K562/ADM cells was much higher than that in K562 cells, and CD34+CD38-CD123+(LSCs)cells in K562/ADM cells was 4-time higher than that in K562 cells. Both P-gp and BCRP were overexpressed in K562/ADM cells relative to K562 cells, about 4% of K562/ADM cells co-expressed P-gp and BCRP,and the content of P-gp+BCRP+ cells was corresponding to that of LSCs in K562/ADM cells. Furthermore, the CD34+ and CD123+ cells expressing BCRP in K562/ADM cells was more than the same cells in K562 cells. Drug-resistant K562/ADM cells displayed 4-fold greater colony-forming ability over the parent K562 cells. CONCLUSIONS: The higher LSC population exists in multidrug-resistant leukemia cells relative to drug-sensitive leukemia cells, and the drug-resistant LSCs are the source of chemotherapy and radiation-therapy resistance of leukemia.
Keywords: Leukemia stem cell Multidrug resistance P-glycoprotein Breast cancer resistance protein Colony formation
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白血病K562/ADM耐药细胞中白血病干细胞及其耐药蛋白的表达
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