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【Cancer research】美沙酮（镇痛药）可杀死白血病
The therapeutic opioid drug methadone (D,L-methadone hydrochloride) is the most commonly used maintenance medication for outpatient treatment of opioid dependence. In our study, we found that methadone is also a potent inducer of cell death in leukemia cells and we clarified the unknown mechanism of methadone-induced cell killing in leukemia cells. Methadone inhibited proliferation in leukemia cells and induced cell death through apoptosis induction and activated apoptosis pathways through the activation of caspase-9 and caspase-3, down-regulation of Bcl-xL and X chromosome–linked inhibitor of apoptosis, and cleavage of poly(ADP-ribose) polymerase. In addition, methadone induced cell death not only in anticancer drug–sensitive and apoptosis-sensitive leukemia cells but also in doxorubicin-resistant, multidrug-resistant, and apoptosis-resistant leukemia cells, which anticancer drugs commonly used in conventional therapies of leukemias failed to kill. Depending on caspase activation, methadone overcomes doxorubicin resistance, multidrug resistance, and apoptosis resistance in leukemia cells through activation of mitochondria. In contrast to leukemia cells, nonleukemic peripheral blood lymphocytes survived after methadone treatment. These findings show that methadone kills leukemia cells and breaks chemoresistance and apoptosis resistance. Our results suggest that methadone is a promising therapeutic approach not only for patients with opioid dependence but also for patients with leukemias and provide the foundation for new strategies using methadone as an additional anticancer drug in leukemia therapy, especially when conventional therapies are less effective. [Cancer Res 2008;68(15):6059–64] 本人已认领该文编译，48小时后若未提交译文，请其他战友自由认领。 Methadone, Commonly Used as Maintenance Medication for Outpatient Treatment of Opioid Dependence, Kills Leukemia Cells and Overcomes Chemoresistance
通常用于阿片依赖患者门诊治疗的维持药物的美沙酮，可以杀死白血病细胞和克服耐药性
The therapeutic opioid drug methadone (D,L-methadone hydrochloride) is the most commonly used maintenance medication for outpatient treatment of opioid dependence.
治疗阿片药物美沙酮(D,L-盐酸美沙酮)通常用于阿片样物质依赖门诊治疗的维持用药。
In our study, we found that methadone is also a potent inducer of cell death in leukemia cells and we clarified the unknown mechanism of methadone-induced cell killing in leukemia cells.
在我们的研究中，我们发现美沙酮也是白血病细胞死亡的强有力的诱导者，我们阐明了在白血病细胞中美沙酮诱导细胞死亡的未知机理。
Methadone inhibited proliferation in leukemia cells and induced cell death through apoptosis induction and activated apoptosis pathways through the activation of caspase-9 and caspase-3, down-regulation of Bcl-xL and X chromosome–linked inhibitor of apoptosis, and cleavage of poly(ADP-ribose) polymerase.
美沙酮抑制白血病细胞增殖和诱导细胞死亡。通过激活半胱氨酸蛋白酶-9和半胱氨酸蛋白酶-3，下调Bcl-xL和x染色体相关凋亡抑制剂，裂解多聚二磷酸腺苷核糖聚合酶，实现凋亡诱导和激活凋亡路径。
In addition, methadone induced cell death not only in anticancer drug–sensitive and apoptosis-sensitive leukemia cells but also in doxorubicin-resistant, multidrug-resistant, and apoptosis-resistant leukemia cells, which anticancer drugs commonly used in conventional therapies of leukemias failed to kill.
此外，美沙酮不仅仅在对抗癌药物敏感和凋亡敏感的白血病细胞中诱导细胞死亡，也在阿霉素耐药、多药耐药、和凋亡抑制的白血病细胞中诱导细胞死亡，抗癌药物通常用于及其难治白血病的常规治疗。
Depending on caspase activation, methadone overcomes doxorubicin resistance, multidrug resistance, and apoptosis resistance in leukemia cells through activation of mitochondria.
依赖于半胱氨酸蛋白酶的激活，美沙酮通过激活线粒体克服了白血病细胞中的阿霉素耐药、多药耐药、和凋亡抑制。
In contrast to leukemia cells, nonleukemic peripheral blood lymphocytes survived after methadone treatment.
与白血病细胞形成对比，非白血病外周血淋巴细胞在美沙酮治疗后仍然存活。
These findings show that methadone kills leukemia cells and breaks chemoresistance and apoptosis resistance.
这些结果表明美沙酮杀死白血病细胞和破坏了耐药性以及凋亡抑制。
Our results suggest that methadone is a promising therapeutic approach not only for patients with opioid dependence but also for patients with leukemias and provide the foundation for new strategies using methadone as an additional anticancer drug in leukemia therapy, especially when conventional therapies are less effective.
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作者:admin@医学,生命科学 2011-05-07 05:14
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