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Sci Trans Med:压力可激活癌细胞,请轻松生活

2017-11-19 佚名 学术经纬

在最新一期的《科学》子刊《Science Translational Medicine》上,来自MD安德森癌症中心的科学家们用精妙的实验验证了这一个假设。他们发现,压力会导致肺癌耐药性的发生,加速癌细胞的生长。

很多人都知道,压力不是个好东西。长期处于压力下的人容易出现一系列疾病,从而形成一个压力恶化病情,病情带来更多压力的恶性循环。

在最新一期的《科学》子刊《Science Translational Medicine》上,来自MD安德森癌症中心的科学家们用精妙的实验验证了这一个假设。他们发现,压力会导致肺癌耐药性的发生,加速癌细胞的生长。而一类缓解压力的常规药物,能够起到增强抗癌药疗效的作用。这个发现对每一个生活在持续压力下的人,都有重要的启迪意义。


▲该研究的负责人John Heymach博士(图片来源:MD安德森癌症中心)

在这项研究中,科学家们选择肺癌作为研究对象。这是一种极为常见和严重的癌症,光在美国每年就有16万名患者。常规的肺癌治疗方法包括了EGFR抑制剂。这类药物在最初往往能对病情起到很好的控制作用。但过了一段时间,癌细胞的EGFR基因往往会出现突变,使原本有效的药物变得无效。患者的病情也会就此复发。

在研究肺癌对EGFR抑制剂产生耐药的过程中,研究人员们发现一种叫做IL-6的免疫信号通路蛋白与之相关。有趣的是,IL-6是一种能被“压力相关激素”所激活的蛋白。这也让研究人员们产生了好奇,决定一探压力信号通路在肺癌耐药过程里扮演的作用。

在培养的细胞中,研究人员们成功构建了对常用EGFR抑制剂产生耐药的模型。往培养基里添加肾上腺素和去甲肾上腺素后,这些压力激素会结合β2肾上腺素受体,激活特定的信号通路,提高IL-6的水平。这会促使癌细胞产生对抗癌药的耐受。


▲该研究的第一作者Monique Nilsson博士(图片来源:MD安德森癌症中心)

“在你身体里感知压力的受体,也同样存在于癌细胞表面,并且能‘激活’这些癌细胞,”该研究的第一作者Monique Nilsson博士说:“有趣的是,在带有EGFR激活突变的非小细胞肺癌细胞里,压力激素对IL-6的诱导效应也越强。我们的数据表明突变的EGFR和β2肾上腺素受体之间的信号存在协同。”

这一现象在小鼠身上也得到了验证。当肿瘤出现EGFR突变后,慢性压力能加快肿瘤的生长。此外,激活β2肾上腺素受体同样能促进对EGFR抑制剂的耐受。这一现象能通过β肾上腺素抑制剂,或是IL-6抑制剂来逆转。这再次证明了压力在肺癌耐药性产生中扮演的作用。

细胞和小鼠实验完成后,研究人员下一步就是检验人体内是否也存在同样的机制。利用现成的3期肺癌临床试验数据,研究人员们做了回顾性的分析。他们发现,那些IL-6水平较高的患者,接受EGFR抑制剂的治疗后,中位总体生存期不容乐观,只有区区4.8个月。而那些IL-6水平较低的患者,中位总体生存期能达到11.5个月!此外,研究人员也证实,β肾上腺素抑制剂的确能起到降低IL-6水平的作用。换句话说,那些缓解压力的药物,也许真的可以延长肺癌患者的生命。

这一点在另一个分析中得到了验证。在一项名为LUX-Lung3的研究中,研究人员注意到,一些使用了EGFR抑制剂的患者,碰巧也使用了β肾上腺素抑制剂。这些患者的中位无进展生存期(疾病不发生进展)为13.6个月,高于没有使用β肾上腺素抑制剂的患者(11.1个月)。

“一般人相信压力对癌症患者是不利的,但癌症的诊断以及必要的治疗也可能为患者带来压力。这些数据暗示,压力激素能直接作用于肿瘤细胞,促进耐药性的生成,”该研究的负责人John Heymach博士说道:“β肾上腺素抑制剂是一类人体耐受良好,而且便宜的药物。它有望改善EGFR靶向疗法效果,前景令人兴奋,我们应当在临床上对这个假设进行检验。”

“如果β肾上腺素抑制剂真的能延缓或者预防EGFR抑制剂耐药性的产生,我们就能给患者口服这些药物。它们耐受良好,而且每天成本只有几美分。这会极大地造福患者。” Heymach博士补充道。

压力影响健康,这一概念又得到了实验结果的支持。我们呼吁,事业虽然重要,但身体才是革命的本钱。在职场拼搏时,请不要忘记劳逸结合,还身心以健康。

原始出处:

Nilsson MB, Sun H, Diao L, et al. Stress hormones promote EGFR inhibitor resistance in NSCLC: Implications for combinations with β-blockers. Sci Tran Med, 2017.

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    2018-06-15 bsmagic9140
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    2017-11-24 孙文杰

    请放松生活.压力有一点点就够了

    0

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    2017-11-21 神功盖世

    学习

    0

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    2017-11-21 yxch36
  5. [GetPortalCommentsPageByObjectIdResponse(id=1656914, encodeId=682a165691446, content=<a href='/topic/show?id=3ca31e71903' target=_blank style='color:#2F92EE;'>#TRA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17719, encryptionId=3ca31e71903, topicName=TRA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=757b24868428, createdName=bsmagic9140, createdTime=Fri Jun 15 00:02:00 CST 2018, time=2018-06-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=263962, encodeId=bbe52639621f, content=请放松生活.压力有一点点就够了, beContent=null, objectType=article, channel=null, level=null, likeNumber=112, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/y1ZJaAFo7AFqm7Hn2QNVTjOpBV9mRicUEjyBqRMnLADF1oQXJGeIVCpiaY1hJVMd1C40EhFCw4LL8sCKTx8Yuvsw/132, createdBy=af0b1960284, createdName=孙文杰, createdTime=Fri Nov 24 15:05:40 CST 2017, time=2017-11-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=263104, encodeId=fa3826310411, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=107, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/fhZdOu27e88Voqh19n8eF8cLplo8L4nicKtH0WnE3KFELXns5XDu8rsiceK2HHDZc2SEStia5VV3Pia2QLMVqlWbHw/0, createdBy=6e012139475, createdName=神功盖世, createdTime=Tue Nov 21 12:55:29 CST 2017, time=2017-11-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1252412, encodeId=eeb312524121c, content=<a href='/topic/show?id=3efee1519b2' target=_blank style='color:#2F92EE;'>#癌细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=117, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71519, encryptionId=3efee1519b2, topicName=癌细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4cea26, createdName=yxch36, createdTime=Tue Nov 21 01:02:00 CST 2017, time=2017-11-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1608268, encodeId=acfd160826898, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=30bd35, createdName=一叶知秋, createdTime=Tue Nov 21 01:02:00 CST 2017, time=2017-11-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=262954, encodeId=1f152629545d, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=113, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/09/27/e6ae4d6996235d5b5d2f416737192359.jpg, createdBy=ba621669454, createdName=麻醉僧, createdTime=Tue Nov 21 00:00:54 CST 2017, time=2017-11-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=262800, encodeId=7d122628003b, content=谢谢分享学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM7GibvIBibibnnnvpajk2stlDF5oichYahI6Bia8uxeTBFoPbdoHWebyXf9eal9FNgUF2lNcrwoZicM3BvQ/0, createdBy=a3742066385, createdName=戒馋,懒,贪, createdTime=Mon Nov 20 10:23:16 CST 2017, time=2017-11-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=262691, encodeId=da7726269138, content=压力致癌, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/fhZdOu27e88Voqh19n8eF8cLplo8L4nicKtH0WnE3KFELXns5XDu8rsiceK2HHDZc2SEStia5VV3Pia2QLMVqlWbHw/0, createdBy=6e012139475, createdName=神功盖世, createdTime=Mon Nov 20 00:47:19 CST 2017, time=2017-11-20, status=1, ipAttribution=)]
    2017-11-21 一叶知秋
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    2017-11-21 麻醉僧

    学习

    0

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    2017-11-20 戒馋,懒,贪

    谢谢分享学习了

    0

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    2017-11-20 神功盖世

    压力致癌

    0

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