美國(guó)研究人員日前發(fā)現(xiàn)一種可以“瞄準(zhǔn)”并殺死癌癥干細(xì)胞的化合物,,在實(shí)驗(yàn)室研究期間,其殺死小鼠身上乳腺癌干細(xì)胞的效力比普通抗癌藥物泰克索(Taxol)高100倍,。
在8月13日發(fā)表在《細(xì)胞》雜志網(wǎng)絡(luò)版上的文章中,,研究人員指出,,他們找到了一種名為鹽霉素(salinomycin)的抗生素,它可以直接殺死癌癥干細(xì)胞,。目前一些科學(xué)家認(rèn)為,,癌癥干細(xì)胞是腫瘤細(xì)胞中數(shù)量比較少但生命力很強(qiáng)的細(xì)胞,它們對(duì)化療和放療有抵抗性,,不容易定位,,還可以“生出”新的腫瘤細(xì)胞,導(dǎo)致癌癥復(fù)發(fā),。正因?yàn)樗鼈兊倪@些特性,,對(duì)付癌癥干細(xì)胞成為治療癌癥的一個(gè)重要課題。
在最新的這項(xiàng)研究中,,研究人員在實(shí)驗(yàn)室中首先制造出大量癌癥干細(xì)胞,,然后用1.6萬種不同的化學(xué)物質(zhì)來對(duì)付它們,試圖從中篩選出有效對(duì)付癌癥干細(xì)胞的化學(xué)物質(zhì),,最終,,科學(xué)家們選定了鹽霉素。
鹽霉素不僅能殺死小鼠身上的乳腺癌干細(xì)胞,,還能抑制它們生出新的腫瘤細(xì)胞,,同時(shí)還能減緩已經(jīng)存在的腫瘤的生長(zhǎng)速度。
目前,,研究人員還需要進(jìn)一步證實(shí)鹽霉素是如何起作用的,,并確定它是否對(duì)人類的腫瘤有效。如果有效,,再經(jīng)過大量研究和實(shí)驗(yàn),,有類似效果的藥品就有可能推向市場(chǎng),這個(gè)過程可能需要數(shù)年或者十幾年,。不過研究人員也認(rèn)為,,這些藥品不太可能對(duì)所有種類的腫瘤細(xì)胞都起作用。
美國(guó)研究人員發(fā)現(xiàn),,鹽霉素能夠殺死乳癌干細(xì)胞,,這相信有助于藥劑公司研制乳癌藥物和療法。
麻省理工學(xué)院和布洛德學(xué)院的研究組員皮育什在電話訪問中說:“有好些證據(jù)顯示,這些細(xì)胞導(dǎo)致病人在療程結(jié)束后再度出現(xiàn)癌病變,。”
他解釋道,,由于癌干細(xì)胞的數(shù)量稀少,而且它們不但可以迅速轉(zhuǎn)化為其他類型的細(xì)胞,,還很難殺滅,,難以在實(shí)驗(yàn)室中研究,因此,,要找到對(duì)付癌干細(xì)胞的物質(zhì)并不容易,,研究組終于辦到了。
研究組在星期四出版的期刊《細(xì)胞》(Cell)發(fā)表的報(bào)告,。他們以大約1萬6000種物質(zhì)來對(duì)付干細(xì)胞,,看哪些物質(zhì)最能殺滅這些干細(xì)胞;結(jié)果,,他們選出了32種物質(zhì),。最終發(fā)現(xiàn),鹽霉素(salinomycin)最強(qiáng),。
研究組在實(shí)驗(yàn)鼠身上使用鹽霉素,,而另一組則注射泰素(taxol,成分為紫杉醇(paclitaxel),。他們比較后發(fā)現(xiàn),,鹽霉素的效用比泰素強(qiáng)100倍。前者體內(nèi)癌干細(xì)胞誘發(fā)乳癌的幾率遠(yuǎn)小于后者,,并且癌病變速度也慢,。
皮育什相信,此法也能用來對(duì)付其他癌腫瘤的干細(xì)胞,。但他說,,鹽霉素能否成為清除乳癌干細(xì)胞的最有效藥物,現(xiàn)今難以說得準(zhǔn),。(生物谷Bioon.com)
生物谷推薦原始出處:
Cell, 13 August 2009 doi:10.1016/j.cell.2009.06.034
Identification of Selective Inhibitors of Cancer Stem Cells by High-Throughput Screening
Piyush B. Gupta1,3,7,,,Tamer T. Onder1,2,7,Guozhi Jiang1,3,Kai Tao4,Charlotte Kuperwasser4,Robert A. Weinberg1,2,6,8,,andEric S. Lander1,2,3,5,8,,
1 Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
2 Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
3 Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
4 Department of Anatomy and Cell Biology, Tufts University School of Medicine and Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA 02111, USA
5 Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
6 MIT Ludwig Center for Molecular Oncology, Cambridge, MA 02139
Screens for agents that specifically kill epithelial cancer stem cells (CSCs) have not been possible due to the rarity of these cells within tumor cell populations and their relative instability in culture. We describe here an approach to screening for agents with epithelial CSC-specific toxicity. We implemented this method in a chemical screen and discovered compounds showing selective toxicity for breast CSCs. One compound, salinomycin, reduces the proportion of CSCs by >100-fold relative to paclitaxel, a commonly used breast cancer chemotherapeutic drug. Treatment of mice with salinomycin inhibits mammary tumor growth invivo and induces increased epithelial differentiation of tumor cells. In addition, global gene expression analyses show that salinomycin treatment results in the loss of expression of breast CSC genes previously identified by analyses of breast tissues isolated directly from patients. This study demonstrates the ability to identify agents with specific toxicity for epithelial CSCs.