加拿大蒙特利尔大学和拉瓦尔大学的科学家发现了一种可使药物直接攻击癌细胞的全新方法，其可为急性骨髓白血病患者等癌症病人带来福音。据科学家称，这种新方法目前已接近于临床试验。相关文章发表在最新出版的《生物化学期刊》（the Journal of Biological Chemistry）上。
研究负责人、蒙特利尔大学药学系教授丁戴尔拉门塔尔表示，他们发现人体中部分类型的细胞存在一个“门口”，如源自骨髓的细胞就存在一个允许博来霉素等抗癌药物进入的“门”，找到并打开这扇“门”就可让药物直接攻击引发白血病的癌细胞。该成果为癌症治疗开辟了一条新途径。
拉门塔尔教授介绍，他在十年前开始将该理论付诸实践，在与人体细胞十分接近的发酵用酵母上进行了试验。目前所获发现正是基于酵母实验的成果，新方法可被应用于人体细胞，并能很快进入临床治疗。
据介绍，新方法对于癌症患者特别是急性骨髓白血病患者实属福音。急性骨髓白血病影响人的白细胞，这种癌症非常难治疗，绝大部分患者对各种抗癌药物没有反应。拉门塔尔教授表示，新方法可以将抗癌药剂以束流的形式治疗急性骨髓白血病。他说：“例如我们发现博来霉素等抗癌药剂对来自患者身上的淋巴瘤细胞具有正面结果，但同时还要依靠‘门口’的存在。”由于博来霉素不表现为免疫抑制剂，他认为这对患者来说是一个十分利好的消息。
拉门塔尔教授还提醒到，新找到的“门口”只存在于部分细胞类型，比如那些来自于骨髓的细胞，但对于乳腺癌等就不起作用，这样就很难使用博来霉素等来治疗乳腺癌患者。因此，他认为目前应着手寻找能够刺激“门口”产生的方式，这样才能够使用博来霉素等药物治疗更多类型的癌症。
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《生物化学期刊》发表论文摘要（英文）
First Published on December 25, 2009, doi: 10.1074/jbc.M109.046151
February 26, 2010 The Journal of Biological Chemistry, 285, 6275-6284.
The Human Carnitine Transporter SLC22A16 Mediates High Affinity Uptake of the Anticancer Polyamine Analogue Bleomycin-A5*
Mustapha Aouida!,1, Richard Poulin§ and Dindial Ramotar!,2
Abstract
Bleomycin is used in combination with other antineoplastic agents to effectively treat lymphomas, testicular carcinomas, and squamous cell carcinomas of the cervix, head, and neck. However, resistance to bleomycin remains a persistent limitation in exploiting the full therapeutic benefit of the drug with other types of cancers. Previously, we documented that the Saccharomyces cerevisiae l-carnitine transporter Agp2 is responsible for the high affinity uptake of polyamines and of the polyamine analogue bleomycin-A5. Herein, we document that the human l-carnitine transporter hCT2 encoded by the SLC22A16 gene is involved in bleomycin-A5 uptake, as well as polyamines. We show that NT2/D1 human testicular cancer cells, which highly express hCT2, are extremely sensitive to bleomycin-A5, whereas HCT116 human colon carcinoma cells devoid of detectable hCT2 expression or MCF-7 human breast cancer cells that only weakly express the permease showed striking resistance to the drug. NT2/D1 cells accumulated fluorescein-labeled bleomycin-A5 to substantially higher levels than HCT116 cells. Moreover, l-carnitine protected NT2/D1 cells from the lethal effects of bleomycin-A5 by preventing its influx, and siRNA targeted to hCT2 induced resistance to bleomycin-A5-dependent genotoxicity. Furthermore, hCT2 overexpression induced by transient transfection of a functional hCT2-GFP fusion protein sensitized HCT116 cells to bleomycin-A5. Collectively, our data strongly suggest that hCT2 can mediate bleomycin-A5 and polyamine uptake, and that the rate of bleomycin-A5 accumulation may account for the differential response to the drug in patients.
