Inhibitory effect of curcumin on MDR1 gene expression in patient leukemic cells
Inhibitory effect of curcumin on MDR1 gene expression in patient leukemic cells
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DOI：
10.1007/bf02973907
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发表时间：
2006-10-01
影响因子：
6.7
通讯作者：
Limtrakul, Pornngarm
中科院分区：
文献类型：
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作者：
Anuchapreeda, Songyot;Thanarattanakorn, Paftra;Limtrakul, Pornngarm
当癌症患者长期接受化疗药物治疗时，一些癌细胞会产生多药耐药（MDR）表型。MDR癌细胞的特征在于编码P-糖蛋白（Pgp）的多药耐药1（MDR 1）基因的过表达，P-糖蛋白是肿瘤细胞的表面蛋白，其功能是产生过度外排，从而导致化疗剂的细胞内浓度不足。各种研究已经寻找有效的MDR调节剂来降低癌细胞中的MDR 1基因表达。我们以前的研究表明，姜黄素在KB-V1多药耐药细胞中表现出MDR调节剂的特征。本研究旨在进一步探讨姜黄素对白血病细胞MDR 1基因表达的影响。白血病细胞收集自2003年7月至2005年2月期间在泰国清迈Maharaj Nakorn清迈医院住院的78名儿童白血病患者。急性淋巴细胞白血病（ALL）61例，急性髓细胞白血病（AML）14例，慢性粒细胞白血病（CIVIL）3例。男47例，女31例，年龄1 ~ 15岁。采集骨髓。分离白血病细胞并在存在或不存在10 μ M姜黄素的情况下培养48小时。RT-PCR检测MDR 1 mRNA水平。结果发现，姜黄素降低了33名患者（42%）细胞中的MDR 1基因表达。姜黄素影响11例复发病例中的5例（45%）、26例药物维持病例中的10例（38%）、18例完成治疗病例中的7例（39%）和23例新患者中的11例（48%）的MDR 1基因表达。与KB-V1细胞相比，白血病患者细胞中MDR 1基因的表达水平被分类为低水平（1-20%）的5例（25%）、中等水平（21-60%）的14例（44%）和高水平（61-100%）的14例（70%）。总之，姜黄素降低了白血病细胞中MDR 1 mRNA的表达，尤其是在MDR 1基因高表达组中。因此，姜黄素治疗可能为未来白血病患者的临床治疗提供一种先导。
When patients with cancers are treated with chemotherapeutic agents a long time, some of the cancer cells develop the multidrug resistance (MDR) phenotype. MDR cancer cells are characterized by the overexpression of multidrug resistance1 (MDR1) gene which encodes P-glycoprotein (Pgp), a surface protein of tumor cells that functions to produce an excessive efflux and thereby an insufficient intracellular concentration of chemotherapeutic agents. A variety of studies have sought potent MDR modulators to decrease MDR1 gene expression in cancer cells. Our previous study has shown that curcumin exhibits characteristics of a MDR modulator in KB-V1 multidrug-resistant cells. The aim of this study was to further investigate the effect of curcumin on MDR1 gene expression in patient leukemic cells. The leukemic cells were collected from 78 childhood leukemia patients admitted at Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand, in the period from July 2003 to February 2005. There were 61 cases of acute lymphoblastic leukemia (ALL), 14 cases of acute myeloblastic leukemia (AML), and 3 cases of chronic myelocytic leukemia (CIVIL). There were 47 males and 31 females ranging from 1 to 15 years old. Bone marrows were collected. The leukemic cells were separated and cultured in the presence or absence of 10 mu M curcumin for 48 hours. MDR1 mRNA levels were determined by RT-PCR. It was found that curcumin reduced MDR1 gene expression in the cells from 33 patients (42%). Curcumin affected the MDR1 gene expression in 5 of 11 relapsed cases (45%), 10 of 26 cases of drug maintenance (38%), 7 of 18 cases of completed treatment (39%), and 11 of 23 cases of new patients (48%). The expression levels of MDR1 gene in leukemic patient cells as compared to that of KB-V1 cells were classified as low level (1-20%) in 5 of 20 cases (25%), medium level (21-60%) in 14 of 32 cases (44%), and high level (61-100%) in 14 of 20 cases (70%). In summary, curcumin decreased MDR1 mRNA level in patient leukemic cells, especially in high level of MDR1 gene groups. Thus, curcumin treatment may provide a lead for clinical treatment of leukemia patients in the future.