Sci Rep:一箭双雕!头痛药竟可阻止三阴性乳腺癌进展!

2018-11-20 Michael,Zoe 转化医学网

近日,来自贝勒大学医学系Ze-Yi Zheng教授领导的研究发现氟桂利嗪(FLN)可以选择性的阻断侵袭性基底样乳腺癌(BLBC)的进展,该研究的最新进展发表于近期的《Scientific Reports》杂志。

导  读

偏头痛那种感觉我相信大家都有体验过,仿佛整个世界都一边倒了。这种痛不欲生的感觉几颗治疗偏头痛的药物就可缓解。但又有谁会想到这些日常随处可见的止痛药会抑制万恶的三阴性乳腺癌呢?!这并不是天方夜谭!近日,来自贝勒大学医学系Ze-Yi Zheng教授领导的研究发现氟桂利嗪(FLN)可以选择性的阻断侵袭性基底样乳腺癌(BLBC)的进展,该研究的最新进展发表于近期的《Scientific Reports》杂志。

先前的研究发现,治疗偏头痛和癫痫的药物可减缓小鼠模型中三阴性乳腺癌的生长。为此,美国和中国的研究人员对这些药物进行了筛选,筛选出可降解N-Ras的现存药物。N-Ras是一种能够促进侵袭性基底样乳腺癌(BLBC)发展的关键蛋白。

该试验筛选出氟桂利嗪(FLN)作为可能抑制三阴性乳腺癌的候选药物,随后的体外研究证实,该药物可选择性地阻断侵袭性基底样乳腺癌细胞的生长,但其并不能不抑制乳腺癌细胞的其他亚型。

贝勒大学医学系Ze-Yi Zheng教授表示,人类有一共有三种RAS基因,H-,N-和K-Ras。超过30%的人类肿瘤含有致癌RAS突变,而K-Ras是癌症中最常见的突变RAS基因,N-Ras突变也发生在某些癌症类型当中。

尽管Ras在癌症中的发挥至关重要的作用,但目前还没有专门针对Ras蛋白的药物问世。一种潜在的治疗途径是通过转录后的蛋白酶水解来控制Ras水平。研究人员设计了一种旨在识别和重新利用FDA批准药物的筛查策略,这些药物可以诱导Ras降解。

该研究团队筛选出钙离子通道阻滞剂氟桂利嗪,其通常用于治疗包括癫痫在内的病症。Ze-Yi Zheng教授,“几十年来,氟桂利嗪在临床中主要用于治疗头晕和眩晕以及预防偏头痛。有趣的是,虽然以前没有使用氟桂利嗪治疗癌症,但先前的研究表明它可以提高癌细胞对某些化疗药物的敏感性”。

该团队随后的研究表明,氟桂利嗪通过自噬诱导N-Ras降解,体外试验表明该药物特异性地抑制了BLBC细胞的生长。通过将氟桂利嗪与靶向N-Ras途径的其他组分的药物组合可以进一步增强这种抑制作用。在最后的实验中,研究人员证明了氟桂利嗪可减少BLBC肿瘤的生长。

研究者承认,需要进一步的研究来确定氟桂利嗪治疗为何以及如何导致BLBC细胞中的N-Ras降解。尽管如此,这项研究证明,小分子抑制剂可以通过自噬途径强制降解Ras,这完全可以作为一种治疗癌症的策略。

他们还指出,这些研究证实了他们使用筛选方法来鉴定和重新利用现有的抗癌药物。Chang教授表示“筛选现有的相对安全的药物的新功能是一种有价值的研究策略,这可能筛选出能够治疗难治疗疾病的药物。研发新型药物耗费太大,利用新型筛选技术可以实现“旧药新用”。

原始出处:Zheng ZY1, Li J1,2, Li F3, et al. Induction of N-Ras degradation by flunarizine-mediated autophagy. Sci Rep. 2018 Nov 16;8(1):16932. 

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    2018-11-21 xlysu
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level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Tue Nov 20 07:58:45 CST 2018, time=2018-11-20, status=1, ipAttribution=)]
    2018-11-20 kafei

    学习了谢谢

    0

  4. 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level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Tue Nov 20 07:58:45 CST 2018, time=2018-11-20, status=1, ipAttribution=)]
    2018-11-20 Y—xianghai

    学习了长知识

    0

  5. 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level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Tue Nov 20 07:58:45 CST 2018, time=2018-11-20, status=1, ipAttribution=)]
    2018-11-20 Y—xianghai

    学习了长知识

    0

  6. 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level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Tue Nov 20 07:58:45 CST 2018, time=2018-11-20, status=1, ipAttribution=)]
    2018-11-20 Y—xianghai

    学习了长知识

    0

  7. 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attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Tue Nov 20 07:59:10 CST 2018, time=2018-11-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=353118, encodeId=87c9353118ca, content=学习了长知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Tue Nov 20 07:59:06 CST 2018, time=2018-11-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=353117, encodeId=f8da35311ee0, content=学习了长知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=17, replyNumber=0, 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level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Tue Nov 20 07:58:45 CST 2018, time=2018-11-20, status=1, ipAttribution=)]
    2018-11-20 Y—xianghai

    学习了长知识

    0

  8. 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level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Tue Nov 20 07:58:45 CST 2018, time=2018-11-20, status=1, ipAttribution=)]
    2018-11-20 Y—xianghai

    学习了长知识

    0

  9. 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level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Tue Nov 20 07:58:45 CST 2018, time=2018-11-20, status=1, ipAttribution=)]
    2018-11-20 Y—xianghai

    学习了长知识

    0

  10. 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    2018-11-20 Y—xianghai

    学习了长知识

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