Moreau Dimitri, Jacquot Catherine, Tsita Polyxeni, Chinou Ioanna, Tomasoni Cristophe, Juge Marcel, Antoniadou-Vyza Ekaterini, Martignat Lionel, Pineau Alain, Roussakis Christos
Laboratoire de Pharmacologie Marine, ISOMer, Faculté de Pharmacie de Nantes, 1 rue Gaston Veil, BP 92208, Nantes Cedex 03, France.
Int J Cancer. 2008 Dec 1;123(11):2676-83. doi: 10.1002/ijc.23809.
Despite our growing insight into carcinogenesis, treatment of tumors, especially nonsmall cell lung cancer (NSCLC), remains limited and it is urgent to develop strategies that target tumor cells and their genetic features. Drug discovery efforts have historically focused on the search for compounds that modulate the protein products of genes. Current drug therapy targets only a few hundred endogenous targets, mainly proteins, such as receptors and enzymes. But now, the interest in specifically targeting RNA is increasing, both for target validation and/or therapeutic purposes. In this regard, our work was concerned with the induction of new molecular targets correlated to a cytostatic effect on NSCLC cell line, after treatment with a new triazin named A190. The in vitro study of cell cycle and apoptosis induction demonstrated the antiproliferative potential of this new compounds, and the use of quantitative RT-PCR analysis permit to display an original mechanism of action involving 2 genes: HEF1 and B2. The antitumor effect was also confirmed by the good results in vivo on nude mice xenografts.
尽管我们对肿瘤发生的认识不断深入，但肿瘤的治疗，尤其是非小细胞肺癌（NSCLC）的治疗仍然有限，因此迫切需要开发针对肿瘤细胞及其基因特征的策略。药物研发工作历来侧重于寻找能够调节基因蛋白质产物的化合物。目前的药物治疗仅针对几百个内源性靶点，主要是蛋白质，如受体和酶。但现在，无论是用于靶点验证还是治疗目的，对特异性靶向RNA的兴趣都在增加。在这方面，我们的工作涉及在用一种名为A190的新型三嗪处理后，诱导与对NSCLC细胞系产生细胞生长抑制作用相关的新分子靶点。细胞周期和凋亡诱导的体外研究证明了这种新化合物的抗增殖潜力，并且使用定量RT-PCR分析能够揭示涉及两个基因（HEF1和B2）的独特作用机制。体内对裸鼠异种移植瘤的良好效果也证实了其抗肿瘤作用。
