NAT MED:含铂化疗剂以介导核糖体合成应激反应的方式杀伤细胞

2017-03-08 wang zhe Med sci

新研究发现奥沙利铂杀伤细胞机理

化疗是除手术、放疗外,癌症治疗的主要手段之一。化疗是惟一的全身性治疗手段。特别是对那些不能手术和放疗的中晚期癌症患者,化疗是惟一有效的治疗手段。顺铂及其它铂化疗药物,如卡铂和奥沙利铂是目前最广泛使用的癌症化疗药物。

含铂化疗药物中顺铂和卡铂主要用于生殖细胞癌症,乳腺癌和恶性肺癌,奥沙利铂属于新的铂类抗癌药,其中铂原子与1,2 二氨环己烷(DACH)及一个草酸基结合。奥沙利铂是单一对映结构体。顺式-草酸(反式-1-1-1,2-DACH)铂。呈白色或类白色冻干疏松块状物,常用于转移性结直肠癌治疗,或辅助治疗原发性肿瘤完全切除后三期(Dukes C)结肠癌其他胃肠癌。在本研究中我们利用独特的多平台遗传学方法来研究临床所使用的铂化疗剂以及最近开发的顺铂类似物的作用机制。经研究显示奥沙利铂与顺铂和卡铂不同,并不通过DNA损伤反应杀死细胞。而是通过诱导核糖体的发生应激以杀伤细胞。药物机制的这种差异解释了奥沙利铂与顺铂在临床用药时的不同,并且可以使我们在应对不同情况的恶性肿瘤时区别用药。这些数据显示出了抗癌一线药物的机理多样性以及根据药物机理不同灵活使用抗癌药物的潜在益处。

原始出处:Bruno P M, Liu Y, Park G Y, et al. A subset of platinum-containing chemotherapeutic agents kills cells by inducing ribosome biogenesis stress. Nature Medicine 2017 Jan 23 doi:10.1038/nm.4291

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    2017-06-13 liye789132251
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    2017-03-10 drj2006
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