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(收稿日期:2007209215)

抗肿瘤药物研究新进展

郑小卫　综述　周黎明　审校

(四川大学华西医学中心基础与法医学院药理学教研室,成都　610041)

The progress of research with antitumor drug

Zheng Xiao 2wei ,Zhou Li 2ming

(Department of Pharmacology ,Preclinical and Forensic Medical School ,West China Medical Center ,Sichuan University ,Chengdu 610041)

摘　要　目的:肿瘤是人体内正在发育的或成熟的正常细胞,在外来和内在有关因素长期作用下,出现过度增生成异常分化

而形成的新生物。它与正常的组织和细胞相比,有一些特异性,肿瘤的靶向治疗常基于此。近年来,随着研究的不断深入,新的观点和治疗思路不断涌现,本文将概述近年来肿瘤研究领域的新进展。

关键词:肿瘤;进展

作者简介:郑小卫,在读硕士生,从事药理学研究

由于环境食品污染的日益加剧,近日公布的2006年城乡居民主要死亡原因统计显示,恶性肿瘤已经成为我国城乡居民的首要死因。攻克和治愈癌症成为当今各国研究的热点,本文将对近年来肿瘤研究领域的进展做一综述。

1　P53与肿瘤

111

内源性P53复活导致肿瘤消退

2002年,美国斯坦福大学研究人员报道,M YC 原癌基因的短暂失活将引起肿瘤消退,即使随后再使其复活也不会恢复细胞的恶性表型,反而会引起凋亡[1]。M YC ,ras ,Bcr 2Abl 原癌基因的关闭都将导致肿瘤细胞凋亡和肿瘤消退[2]。那么抑癌基因的复活会不会影响肿瘤的生长?p53蛋白是声名显赫的肿瘤抑制蛋白。大约一半以上的人类肿瘤中都发现有突变的p53。研究人员已经找到少量可恢复p53功能的成分,但直到现在,这些活性成分是否能逆转原发性肿瘤生长一直没有实验证据。冷泉港实验室的研究人员对此做了研究。他们利用四环素调节的短发夹结构p53建立条件复活型嵌合体小鼠模型,这种模型的p53处于失活状态,给于多西环素(doxycycline ,四环素类抗生素)后p53复活。研究发现在淋巴瘤,肝癌肿瘤和恶性肉瘤上都发生了p53引起的肿瘤消退,其消退的范围在40%2100%,即使p53短暂复活后随即失活也能引起肿瘤的消退[3]。

麻省理工大学癌症研究中心的研究小组也对此做了研究。他们采用RNA 干涉条件性调节内源性p53在肝癌小鼠中的表达,结果发现即使内源性p53短暂激活都能引起p53缺失肿瘤的完全消退,p53引起的不是凋亡,而是细胞衰老,并且上调炎症因子,引起天然免疫系统攻击肿瘤细胞[4]。

肿瘤消退是怎么发生的?其机制是什么?进一步的研究发现淋巴瘤是通过细胞凋亡,而恶性肉瘤和肝脏肿瘤则是通过