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Open Biol:抗氧化剂对癌症患者有害

2013-01-22 Open Biol 医师报

  近日,曾因发现DNA双螺旋结构而分享诺贝尔医学与生理学奖的Jim Watson教授公布了一个有关活性氧分子(ROS)的假说,认为肿瘤细胞内的抗氧化物水平与肿瘤细胞耐药有关。换句话说,含有抗氧化剂(包括β-胡萝卜素、维生素A、C和E以及硒等)的营养品对肿瘤患者有害。(Open Biol.2013年1月8日在线版)   Watson指出,用来直接杀死肿瘤细胞的绝大多数药物或物

  近日,曾因发现DNA双螺旋结构而分享诺贝尔医学与生理学奖的Jim Watson教授公布了一个有关活性氧分子(ROS)的假说,认为肿瘤细胞内的抗氧化物水平与肿瘤细胞耐药有关。换句话说,含有抗氧化剂(包括β-胡萝卜素、维生素A、C和E以及硒等)的营养品对肿瘤患者有害。(Open Biol.2013年1月8日在线版)

  Watson指出,用来直接杀死肿瘤细胞的绝大多数药物或物质,包括电离辐射、大多数化疗药物、部分靶向治疗药物,可通过间接或直接产生ROS来阻碍细胞生长周期的关键步骤。这些治疗手段在产生ROS的同时,为肿瘤细胞提供了缺氧环境,从而促使肿瘤细胞从上皮细胞向间充质细胞转化。在肿瘤细胞进化过程中,它们可产生抗氧化蛋白(包括谷胱甘肽、超氧化物歧化酶、过氧化氢酶和硫氧还蛋白),阻碍抗癌治疗发挥作用。一旦肿瘤细胞对化疗药物不敏感,意味着电离辐射治疗也无效。

  此外,转化后的肿瘤细胞可产生能自由移动的间充质细胞,后者可灵活地移动,进而促使肿瘤细胞转移至其他部位,例如肝脏、大脑和肺脏等。幸运的是,广泛应用的降糖药物二甲双胍能优先杀死间充质细胞,这在近年发表的相关研究中得到了验证。

  Watson表示,主要由RAS和Myc驱动的肿瘤是最难以治疗的肿瘤,因为这些肿瘤细胞含有高水平的可破坏ROS的抗氧化物质,这也许能解释为什么胰腺癌很难治疗。若这一理论被证实,则可降低肿瘤细胞内抗氧化物质水平的药物会对上述肿瘤有效。事实上,目前用于粒细胞性白血病的三氧化二砷就可降低谷胱甘肽和硫氧还蛋白水平。如此看来,三氧化二砷可能对其他肿瘤也有疗效。

  Watson指出,该理论的启示意义还在于,我们之前认为有防癌和抗癌作用的含有抗氧化剂的营养品可能对肿瘤患者有害。事实上,许多营养干预研究也显示,这些含抗氧化物质的营养品无助预防胃肠道肿瘤或延长肿瘤患者寿命。

  美国癌症治疗中心主任Maurie Markman指出,“这是一个很复杂的过程”;其次,抗氧化物质是我们正常饮食的组成部分;另外,采用简单的方法将体内的抗氧化物质去除不太可能成为抗肿瘤治疗的有用策略。



Abstract
The vast majority of all agents used to directly kill cancer cells (ionizing radiation, most chemotherapeutic agents and some targeted therapies) work through either directly or indirectly generating reactive oxygen species that block key steps in the cell cycle. As mesenchymal cancers evolve from their epithelial cell progenitors, they almost inevitably possess much-heightened amounts of antioxidants that effectively block otherwise highly effective oxidant therapies. Also key to better understanding is why and how the anti-diabetic drug metformin (the world's most prescribed pharmaceutical product) preferentially kills oxidant-deficient mesenchymal p53− −cells. A much faster timetable should be adopted towards developing more new drugs effective against p53− − cancers.    

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    2013-10-08 sunylz
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    2013-06-05 feather89
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