好的,各位朋友大家好,欢迎收听本期的《科学播报》。癌症是人类的一大顽疾。为了攻克癌症,科学家们一边在寻找全新的疗法,一边在尝试让现有的抗癌药物变得更有效。
白血病是儿童中常见的癌症。它的治愈率相对较高,相关的疗法也得到了比较充分的开发。其中,甲氨蝶呤是一种经典的白血病治疗药物。它能抑制四氢叶酸 的合成,让癌细胞无法合成DNA和蛋白质,从而杀死癌细胞。但这种药物也会影响到正常细胞,从而带来巨大的毒性。如果能找到提高这种药物效果的方法,或许我们就能对患者使用更低的剂量,在维持疗效的同时,降低它带来的副作用。
为了寻找到有潜力提高甲氨蝶呤效果的基因,来自麻省理工学院的一支科研团队进行了一场基因组层面的深度筛选。这项研究成果发表在了科学期刊《自然》上。研究人员利用先进的研究技术,在对甲氨蝶呤高度敏感的癌细胞中,寻找造成这种敏感性的基因。其中,一条叫做FTCD的基因吸引了研究人员们的关注。
该基因编码了一种组氨酸分解代谢所必需的酶,而组氨酸则是人体所必需的氨基酸之一。研究人员们在癌细胞中移除了几个参与组氨酸分解代谢的酶,而后续的观察验证了他们的筛选结果——一旦组氨酸无法顺利代谢,甲氨蝶呤的效果就大打折扣。而如果突破组氨酸代谢中的限制因素,加速它的分解,甲氨蝶呤的疗效就会增加。在人体相关性研究中,那些组氨酸代谢水平较高的病患,生存率也较高。
可是,为什么组氨酸能提高抗癌药的效果呢?在生化途径上做了一系列研究的科学家们发现,原来组氨酸分解的通路上,竟然有四氢叶酸的参与。而FTCD正是调控这一步骤的酶,能将四氢叶酸转化成谷氨酸。
也就是说,抗癌药甲氨蝶呤能抑制四氢叶酸的合成,而FTCD能加速四氢叶酸的代谢。一进一出,细胞里的四氢叶酸很快就陷入了枯竭。缺乏了四氢叶酸,癌细胞自然就得到了抑制。
那么,有什么办法能加速消耗四氢叶酸呢?方法有,而且很简单——在饮食中添加组氨酸。细胞内的组氨酸水平越高,其代谢就越活跃,而四氢叶酸代谢也会得到加速。
在小鼠实验中,这一简单的设想,起到了极好的效果。在饮食中添加少量组氨酸后,极大地提高了甲氨蝶呤的疗效。
接下来,研究人员们期望能在人体中重复这一结果。组氨酸在常见的肉类食物中都很普遍。如果这些食物能改善抗癌药的效果,减少抗癌药的副作用,无疑将是全世界白血病患者的福音。
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