典型的癌癥治療藥物能夠殺死大多數(shù)的白血病細(xì)胞（左）,，但是依然有一些癌細(xì)胞能夠活下來(lái)（右）。而美沙酮?jiǎng)t能夠做到一個(gè)不剩,。（圖片提供: Claudia Friesen, University of Ulm, Germany）
一項(xiàng)新的研究表明,，那些用來(lái)抑制海洛因毒癮的藥物竟然能夠殺死白血病細(xì)胞。研究人員發(fā)現(xiàn),，美沙酮——一種有效的合成麻醉藥,，不像嗎啡或海洛因那樣容易讓人上癮，在戒毒治療中被用作這些毒藥的替代品——能夠破壞對(duì)化學(xué)療法具有抗性的癌細(xì)胞,，同時(shí)又不會(huì)對(duì)健康細(xì)胞造成影響,。但是一個(gè)最關(guān)鍵的問(wèn)題就是，這項(xiàng)實(shí)驗(yàn)室研究結(jié)果能否轉(zhuǎn)化為針對(duì)癌癥病人的有效治療,。
美沙酮通過(guò)與大腦中的阿片受體結(jié)合而產(chǎn)生作用,。這時(shí)，它會(huì)妨礙其他毒品——例如海洛因——到達(dá)阿片受體,，由此而抑制由毒癮產(chǎn)生的對(duì)毒品的強(qiáng)烈渴望,。1999年，美沙酮能夠作為一種抗癌藥物的想法浮出水面——研究人員當(dāng)時(shí)發(fā)現(xiàn),，這種消除毒癮的藥物居然在實(shí)驗(yàn)室測(cè)試中殺死了肺癌細(xì)胞,。
德國(guó)烏爾姆大學(xué)的分子生物學(xué)家Claudia Friesen最近發(fā)現(xiàn),，美沙酮對(duì)白血病細(xì)胞也能夠產(chǎn)生作用，并最終導(dǎo)致后者的死亡,。Friesen和她的研究小組用30,、20、15和10微摩爾每升濃度的美沙酮對(duì)白血病細(xì)胞和健康的人類(lèi)血液細(xì)胞進(jìn)行了處理,。結(jié)果顯示,，在48小時(shí)之后，濃度最高的美沙酮幾乎殺死了全部的癌細(xì)胞,，與此同時(shí),，那些健康的血液細(xì)胞卻無(wú)一受損——后者缺乏與美沙酮結(jié)合所需要的特定受體。而在另一項(xiàng)實(shí)驗(yàn)中,，研究人員發(fā)現(xiàn),，美沙酮還能夠殺死通常對(duì)另一些化療藥物具有抗性的白血病細(xì)胞。研究人員在8月1日出版的《癌癥研究》（Cancer Research）雜志上報(bào)告了他們的這項(xiàng)研究成果,。
Friesen表示,，研究人員下一步將在動(dòng)物模型中測(cè)試美沙酮，從而搞清這種藥物是否還能夠治療其他類(lèi)型的癌癥,，以及更好地了解其副作用,。但是美國(guó)明尼蘇達(dá)州羅徹斯特市梅奧醫(yī)療中心的細(xì)胞藥理學(xué)家Scott Kaufmann對(duì)于美沙酮能夠用于癌癥治療表示懷疑。Kaufmann指出,，這種藥物殺死白血病細(xì)胞所需要的劑量——30微摩爾每升——對(duì)人類(lèi)而言是有害的,。因此他說(shuō)，除非研究人員能夠克服副作用,，“否則美沙酮只能是一個(gè)讓人干著急的想法,，就像它對(duì)肺癌細(xì)胞做的那樣。我不認(rèn)為這一發(fā)現(xiàn)具有重大的實(shí)際意義”,。（生物谷Bioon.com）
生物谷推薦原始出處：
Cancer Research,，68, 6059-6064,，Claudia Friesen,，Erich Miltner
Methadone, Commonly Used as Maintenance Medication for Outpatient Treatment of Opioid Dependence, Kills Leukemia Cells and Overcomes Chemoresistance
Claudia Friesen, Mareike Roscher, Andreas Alt and Erich Miltner
Institute of Legal Medicine, University of Ulm, Ulm, Germany
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]
