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BMCVR:癌症“老”药的“新”用途

新药编辑:新特药 更新时间:2015-04-14

2015年4月14日 讯 /tumor.net.cn/ --治疗白血病很多年的药物或许还可以抵御其它的癌症,近日来自密苏里大学就阐述了老药新用的癌症治疗策略,此前医生们利用6-硫鸟嘌呤(6-TG)来作为一种化疗方法杀灭白血病患者机体的癌细胞,而近些年很多医生开始利用更加有用的新型药物来替代6-TG的使用了,如今研究者Jeffrey Bryan表示,我们发现6-TG不仅可以杀灭癌细胞,而且其还可以改变特定癌细胞的功能,削弱其侵袭性从而使得其可以被药物杀灭。

机体中的每一个细胞都具有特定的遗传特性,称之为表观遗传特性,其可以给予细胞指令让其发挥作用,告诉其什么时候增殖,什么时候死亡等。而癌细胞拥有的表观遗传标志物可以促进基因要么被关闭要么失去控制,这就会促进癌细胞无限增殖,最后难以被杀灭,进而损伤机体健康组织。

文章中研究者发现6-TG可以通过去甲基化的作用来影响癌细胞的表观遗传标记物,去甲基化作用可以关闭一些损坏的表观遗传标记物,同时又会开启那些促进细胞扮演健康方式的标志物,该研究发现或可帮助科学家们利用多种药物来开发新型的癌症疗法。

研究者Bryan说道,当6-TG不再强有力地作为杀灭癌细胞的药物时,研究者又发现其如果联合其它药物则又会重新具有抑制癌症的效力,如果可以利用6-TG来关闭癌细胞中的危险标志物,那么这些癌细胞就会很容易被杀灭,随后研究者就可以利用特殊的抗癌药物来清除癌细胞。

相关研究发表于国际杂志BMC Veterinary Research上,研究者指出,研究的早期阶段是非常有希望的,如果进行额外的实验,包括动物实验等,或许就可以在数年之后成功,这样研究者就可以向联邦政府递交申请来开始进行人类的药物试验,随后他们就将同世界上其它的肿瘤学家联合开展研究开发新型的癌症疗法。(tumor.net.cn)

doi:10.1186/s12917-014-0290-8
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6-Thioguanine and zebularine down-regulate DNMT1 and globally demethylate canine malignant lymphoid cells

Brian K Flesner12, Senthil R Kumar1 and Jeffrey N Bryan1*

Background The antimetabolite 6-thioguanine (6-TG) has been used to treat both human and canine lymphoid malignancies. 6-TG has been shown to be epigenetically active as a demethylating agent in a human lymphoma cell line, causing downregulation of DNA methyltransferase 1 (DNMT1) through ubiquitin-targeted degradation. Zebularine (Zeb), a similar cytidine analog, also has demethylating activity as well as oral bioavailability. The hypothesis of the present study was that 6-TG and Zeb would cause downregulation of DNMT1 and globally demethylate the genomic DNA of canine lymphoma cells. The secondary hypothesis was that these agents would cause a dose-dependent decrease in cell proliferation in canine lymphoma cells. Canine CLGL-90 malignant T cells and CLL 17–7 cells were incubated in modified RPMI media. They were treated with 6-TG, Zeb, or control media at biologically relevant concentrations. Results Following treatment with each agent, DNMT1 protein and global DNA methylation were significantly decreased. A dose-dependent decrease in cell survival was also observed, with apoptosis being the primary mode of cell death in the CLGL-90 cell line. Conclusions These results confirm the demethylating action of 6-TG and Zeb in canine cells which is similar to that shown in human cell lines. Confirmation of this mechanism supports the clinical application of these compounds as demethylating drugs in veterinary patients.

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