來自斯坦福大學(xué)Stanley N. Cohen博士實(shí)驗(yàn)室的Chih-Jian Lih和其他研究人員確定出了一個(gè)影響人類癌細(xì)胞對(duì)化療敏感性的基因,。該發(fā)現(xiàn)將有助于研究人員改善化療的治療效果,。這項(xiàng)研究的相關(guān)文章將刊登在8月1日的Gene & Development雜志上,。
利用一種能隨機(jī)改變哺乳動(dòng)物細(xì)胞基因表達(dá)的方法和能檢測(cè)改變的基因功能的篩選方法,，Cohen博士和同事確定出之前從未確定出的基因txr1,。前列腺癌細(xì)胞中這個(gè)基因表達(dá)的增加會(huì)導(dǎo)致對(duì)taxane藥物的抗性,。Taxanes是一類廣泛使用的化療藥物,，商品名為docetaxel和paclitaxel,。這類藥物能夠通過抑制微管降解和之后細(xì)胞分裂來阻止癌細(xì)胞的生長,。
研究人員確定出txr1能夠通過抑制抗血管形成和促凋亡因子thrombospondin 1（TSP-1）來促進(jìn)taxane藥物抗性的發(fā)生。這種作用完全不同于之前發(fā)現(xiàn)的與taxanes抗性有關(guān)的作用機(jī)制,。
研究人員還進(jìn)一步發(fā)現(xiàn)txr1的刪除或用TSP-1處理,，能夠恢復(fù)癌細(xì)胞對(duì)taxane藥物的敏感性。由于獲得性藥物抗性是限制了taxanes的長期效果,，因此txr1的發(fā)現(xiàn)為調(diào)節(jié)化療藥物的反應(yīng)和敏化癌細(xì)胞對(duì)藥物治療的應(yīng)答開辟了新的途徑,。
英文原文：
Novel mechanism of taxane resistance
Research Associate Chih-Jian Lih and others working in the laboratory of Dr. Stanley N. Cohen at Stanford University have pinpointed a gene that affects human cancer cells' sensitivity to chemotherapy - an important finding in the effort to increase the effectiveness of chemotherapy.
Their paper will be published online in advance of its scheduled August 1 publication date (www.genesdev.org).
Using an approach that randomly alters expression of mammalian cell genes, together with a screen that detects altered gene function, Dr. Cohen and colleagues identified a previously uncharacterized gene, called txr1, whose increased expression in prostate cancer cells confers resistance to taxane drugs. Taxanes are a class of widely-used chemotherapeutics (marketed as docetaxel and paclitaxel) that prevent cancer cell growth by inhibiting microtubule breakdown and subsequent cell division.
The researchers determined that txr1 promotes taxane resistance by suppressing the known anti-angiogenic and pro-apoptotic factor, thrombospondin 1 (TSP-1). This action is entirely different from mechanisms found earlier to be involved in resistance to taxanes.
Furthermore, they discovered that depletion of txr1, or treatment with TSP-1 (or a TSP-1 mimetic) restores taxane sensitivity. As acquired drug resistance poses a major limitation to the long-term efficacy of taxanes, the discovery of txr1 as a component of a novel pathway of taxane cytotoxicity opens up a new avenue to modulate chemotherapeutic drug response and sensitize cancer cells to drug treatment.
