加拿大蒙特利爾大學(xué)和拉瓦爾大學(xué)的科學(xué)家發(fā)現(xiàn)了一種可使藥物直接攻擊癌細(xì)胞的全新方法,，其可為急性骨髓白血病患者等癌癥病人帶來(lái)福音。據(jù)科學(xué)家稱,，這種新方法目前已接近于臨床試驗(yàn),。相關(guān)文章發(fā)表在最新出版的《生物化學(xué)雜志》上。
研究負(fù)責(zé)人,、蒙特利爾大學(xué)藥學(xué)系教授丁戴爾·拉門塔爾表示,，他們發(fā)現(xiàn)人體中部分類型的細(xì)胞存在一個(gè)“門口”，如源自骨髓的細(xì)胞就存在一個(gè)允許博來(lái)霉素等抗癌藥物進(jìn)入的“門”,，找到并打開這扇“門”就可讓藥物直接攻擊引發(fā)白血病的癌細(xì)胞,。該成果為癌癥治療開辟了一條新途徑。
拉門塔爾教授介紹,，他在十年前開始將該理論付諸實(shí)踐,，在與人體細(xì)胞十分接近的發(fā)酵用酵母上進(jìn)行了試驗(yàn)。目前所獲發(fā)現(xiàn)正是基于酵母實(shí)驗(yàn)的成果,，新方法可被應(yīng)用于人體細(xì)胞,，并能很快進(jìn)入臨床治療。
據(jù)介紹,，新方法對(duì)于癌癥患者特別是急性骨髓白血病患者實(shí)屬福音,。急性骨髓白血病影響人的白細(xì)胞，這種癌癥非常難治療,，絕大部分患者對(duì)各種抗癌藥物沒(méi)有反應(yīng),。拉門塔爾教授表示，新方法可以將抗癌藥劑以束流的形式治療急性骨髓白血病,。他說(shuō)：“例如我們發(fā)現(xiàn)博來(lái)霉素等抗癌藥劑對(duì)來(lái)自患者身上的淋巴瘤細(xì)胞具有正面結(jié)果,，但同時(shí)還要依靠‘門口’的存在。”由于博來(lái)霉素不表現(xiàn)為免疫抑制劑,，他認(rèn)為這對(duì)患者來(lái)說(shuō)是一個(gè)十分利好的消息,。
拉門塔爾教授還提醒到，新找到的“門口”只存在于部分細(xì)胞類型,，比如那些來(lái)自于骨髓的細(xì)胞,，但對(duì)于乳腺癌等就不起作用，這樣就很難使用博來(lái)霉素等來(lái)治療乳腺癌患者,。因此,，他認(rèn)為目前應(yīng)著手尋找能夠刺激“門口”產(chǎn)生的方式,，這樣才能夠使用博來(lái)霉素等藥物治療更多類型的癌癥。（生物谷Bioon.com）
生物谷推薦原文出處：
JBC doi: 10.1074/jbc.M109.046151
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
1 Awarded a post-doctoral fellowship from the National Cancer Institute of Canada. To whom correspondence may be addressed: 5415 de l'Assomption, Montreal, QC, Canada, H1T 2M4.
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.
