活性小分子提高Par-4水平的研究进展

Research Progress of Active Small Molecules Increasing Level of Par-4

新兴的化疗药使肿瘤治疗从传统的细胞毒性药物治疗时代跨越到精准分子靶向治疗时代。在众多促凋亡抑癌基因中,前列腺凋亡反应基因-4编码的前列腺凋亡反应蛋白-4(Par-4)与肿瘤细胞表面过表达受体——葡萄糖调节蛋白78结合,通过胞内线粒体凋亡途径、死亡受体凋亡途径和胞外旁分泌通路共同诱导肿瘤细胞凋亡而不进攻正常细胞,在体外和体内显示出良好的抗肿瘤活性,无明显的细胞和全身毒性。来源于植物和微生物衍生物以及人工合成的活性小分子可调节Par-4水平,这些活性小分子通过结合细胞内的波形蛋白,将Par-4从波形蛋白中置换出来,从而发挥抗肿瘤活性。但目前关于这类活性小分子的报道较少,未来应进行深入研究。

Emerging chemotherapeutics have allowed tumor treatment to leap from the traditional cytotoxicera to the era of precise molecular targeting.Prostate apoptosis response gene-4 is one of the promising tumor suppressor genes among the many studies on pro-apoptotic tumor suppressor genes.The encoded prostate apoptosis response protein-4(Par-4)binds to its overexpressed receptor-glucose-regulated protein 78 on the surface of tumor cells,and induces tumor cell apoptosis without attacking normal cells,through mitochondrial apoptotic pathway,death receptor apoptotic pathway and extracellular paracrine pathway jointly,and shows good anti-cancer activity in vitro and in vivo,without obvious cellular and systemic toxicity.The level of Par-4 can be regulated by plant and microbial derivatives and synthetic active small molecules.These active small molecules replace Par-4 from vimentin by binding to vimentin in cells,so as to exert their antitumor activity.However,there are few reports on this kind of active small molecules,which should be further studied in the future.