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研究发现决定癌细胞化疗效果的基因

2018-07-18

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导读:来自斯坦福大学StanleyN.Cohen博士实验室的Chih-JianLih和其他研究人员确定出了一个影响人类癌细胞对化疗敏

  来自斯坦福大学Stanley N. Cohen博士实验室的Chih-Jian Lih和其他研究人员确定出了一个影响人类癌细胞对化疗敏感性的基因。该发现将有助于研究人员改善化疗的治疗效果。这项研究的相关文章将刊登在8月1日的Gene & Development杂志上。

  利用一种能随机改变哺乳动物细胞基因表达的方法和能检测改变的基因功能的筛选方法,Cohen博士和同事确定出之前从未确定出的基因txr1。前列腺癌细胞中这个基因表达的增加会导致对taxane药物的抗性。Taxanes是一类广泛使用的化疗药物,商品名为docetaxel和paclitaxel。这类药物能够通过抑制微管降解和之后细胞分裂来阻止癌细胞的生长。

  研究人员确定出txr1能够通过抑制抗血管形成和促凋亡因子thrombospondin 1(TSP-1)来促进taxane药物抗性的发生。这种作用完全不同于之前发现的与taxanes抗性有关的作用机制。

  研究人员还进一步发现txr1的删除或用TSP-1处理,能够恢复癌细胞对taxane药物的敏感性。由于获得性药物抗性是限制了taxanes的长期效果,因此txr1的发现为调节化疗药物的反应和敏化癌细胞对药物治疗的应答开辟了新的途径。

  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.

[关键词: 癌细胞 基因 ]

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