Cancer Res:科学家终于找到了运动抗乳腺癌的机制,每周150分钟运动或真有助于抗癌

2017-09-13 朱爽爽 奇点网

相信,大部分患者在被确诊为癌症时,在经历了短暂的伤心和绝望后,都会寻求积极治疗。因为他们心中都抱有一丝希望,说不定会有奇迹出现。然而,在他们寻求各种积极治疗的过程中,有一种既廉价,又有效而且副作用还小的方案却被大多数人遗忘了,这一方案就是“运动”。

相信,大部分患者在被确诊为癌症时,在经历了短暂的伤心和绝望后,都会寻求积极治疗。因为他们心中都抱有一丝希望,说不定会有奇迹出现。然而,在他们寻求各种积极治疗的过程中,有一种既廉价,又有效而且副作用还小的方案却被大多数人遗忘了,这一方案就是“运动”。



乳腺癌为例,已有大量研究表明,经常运动的人群,乳腺癌的发病风险比较少运动的人群降低了近30%。同样的,对于确诊为乳腺癌的患者来说,在确诊后经常锻炼的患者,其全因死亡率更是降低了近50%,而归因于乳腺癌的死亡率也降低了近30%。此外,美国还将运动纳入了乳腺癌的标准治疗指南中,建议乳腺癌患者每周进行150分钟左右的中等强度锻炼。

说到这,可能仍然有人怀疑运动抗癌的可行性,因为上述关于运动与乳腺癌之间的研究只是相关性研究。也有可能是经常锻炼的人具有更好的生活条件或者作息规律,因此其发病风险以及死亡风险才较低的。而现在,来自丹麦的科学家们首次发现了运动抑制乳腺癌的具体的分子机制,进一步证明了运动真的可以抗癌!

近日,来自丹麦哥本哈根大学炎症与代谢研究中心以及身体活动中心的Pernille Hojman博士在美国癌症研究协会旗下的杂志《癌症研究》上发表的一篇论文表明,运动之所以能够发挥抗乳腺癌作用,是因为运动过程中产生的肾上腺素可以激活经典的抑癌通路,Hippo信号通路,引起癌细胞生长,转移,耐药所必须的YAP蛋白失活。


Hojman博士

虽然此前关于乳腺癌与运动的大量相关性研究都表明,运动与乳腺癌发生,复发以及死亡风险的降低相关。但是关于其中的具体机制很少有人研究。仅在2008年的时候,一些学者提出,运动降低乳腺癌的风险可能是由于长期的运动可以减少各种癌症的风险因素,例如肥胖、慢性炎症等等。

然而,2016年的时候,Hojman博士的研究团队意外发现,并不需要长期运动,仅单次运动就可以产生明显的抗癌作用,表现为,仅凭单次运动后的血清就能使乳腺癌细胞的增殖活性降低了10%。这一发现引起了Pernille Hojman博士对运动抗癌现象的强烈兴趣,也促使其对这一现象进行系统的研究,以确定其具体机制。

为此,在之前实验的基础上,Hojman博士选择了两种常见的乳腺癌细胞系,MCF-7(激素受体阳性乳腺癌细胞)以及MDA-MB-231(三阴性乳腺癌细胞系)。同时,Hojman博士让参与实验的20名乳腺癌妇女以及正常妇女同时进行2小时的中等强度的运动,然后提取运动前和运动后的血清,并分别与上述两种乳腺癌细胞一起培养。

结果,同Hojman博士2016年的研究结果相符,无论是乳腺癌妇女还是正常妇女,相比与运动前,运动后的血清都能使上述两种细胞的增殖活性降低10%-20%。这意味着,无论是正常妇女还是乳腺癌妇女,运动都可以产生明显的抗癌作用。


电镜下的乳腺癌细胞

而为了进一步确定运动产生抗癌作用的能力。Hojman博士还将500万个MCF-7细胞或者MDA-MB-231细胞分别与运动前或者运动后健康妇女的血清一同培养48小时,然后移植进入裸鼠体内,以研究运动抑制乳腺癌发生的能力。

结果,Hojman博士惊喜的发现,与运动前的血清一起培养的MCF-7细胞在90%的裸鼠体内形成了肿瘤,而与运动后血清一起培养的MCF-7细胞仅在45%的裸鼠体内形成了肿瘤。同时,相比于运动前的血清,与运动后血清一起培养的MCF-7细胞在裸鼠体内形成的肿瘤大小更是减少了76%。

同样地,对于MDA-MB-231细胞来说,相比于运动前的血清,运动后的血清使MDA-MB-231细胞在裸鼠中形成肿瘤的能力降低了20%,然而二者形成肿瘤的大小并没有区别。表明,运动不仅可以抑制乳腺癌细胞的增殖,还能显着减弱其形成肿瘤的能力。特别地,运动对于MCF-7细胞的抑制能力更强。

那么运动是如何发挥抗癌作用的呢?结合之前的研究,Hojman博士发现,原来人们在运动过程中产生的大量的肾上腺素等儿茶酚胺类激素才是真正的“抗癌先锋”。它们可以激活Hippo抑癌信号通路,导致YAP蛋白的磷酸化失活(已知YAP蛋白是癌细胞生长、增殖、转移与耐药所必需的一种蛋白),从而发挥抗癌作用的。

最后,Hojman博士还在MCF-7细胞以及MDA-MB-231细胞移植的小鼠肿瘤模型体内直接测试了肾上腺素以及去甲肾上腺素的抗癌活性。通过每天给小鼠注射少量的肾上腺素或者去甲肾上腺素,Hojman博士发现,每天适量肾上腺素的注射可以使MCF-7细胞移植裸鼠的肿瘤生长速度降低85%,MDAMB-231细胞移植裸鼠的肿瘤生长速度降低59%。同样地,去甲肾上腺素同样能使MCF-7细胞移植裸鼠的肿瘤生长速度降低53%,使MDAMB-231细胞移植裸鼠的肿瘤生长速度降低58%。

虽然,Hojman博士的研究证明了运动抗癌是可行的。但是并不鼓励乳腺癌患者私下进行锻炼。

正如Hojman博士所说,“虽然,这项研究的结果表明,中度至高强度运动可以使机体肾上腺素水平的急剧增加,通过激活Hippo信号通路降低乳腺癌细胞的生长活性,表明乳腺癌女性进行中度至高强度的运动可能有助于癌症的治疗。但是,由于锻炼方案需要根据病人的身体情况制定,因此,被诊断患有乳腺癌的妇女应在开始锻炼计划前仔细咨询医生。”

此外,Hojman博士还计划在今年秋天招募乳腺癌患者,在为期12周的新辅助化期间进行随机对照运动干预研究,以进一步研究运动训练对乳腺癌患者的术后并发症的影响,以及完善运动抗癌的方案。

原始出处:Dethlefsen C, Hansen LS, Lillelund C, et al. Exercise-Induced Catecholamines Activate the Hippo Tumor Suppressor Pathway to Reduce Risks of Breast Cancer Development. Cancer Res. 2017 Sep 8. 

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    2017-09-15 wxl882001

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    2017-09-15 sunfeifeiyang

    学习

    0

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    2017-09-14 133****4869

    学习了

    0

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    2017-09-14 1881fe7befm

    这篇文章得仔细拜读.从中学习实验设计.从中能不能找出新的研究方向!

    0

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    2017-09-14 sunfeifeiyang

    运动包治百病

    0

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    2017-09-14 执着追梦

    学习.谢谢分享

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=244334, encodeId=6df624433465, content=学习一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6KcicAVC1MwuOgo3iaicb1Imgk1yIfnvr6oXzibcAFB6puAyNJXbzWhNuLqaFYBVRWjh7rghkvFLPxMAfD5ib3nXwVD/0, createdBy=bed21972958, createdName=wxl882001, createdTime=Fri Sep 15 15:19:09 CST 2017, time=2017-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=244215, encodeId=568b24421573, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/09/07/a9772c74ffd6edc03a7f9af07b4747f6.jpg, createdBy=b3722138742, createdName=sunfeifeiyang, createdTime=Fri Sep 15 07:54:03 CST 2017, time=2017-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=243990, encodeId=c60824399050, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2017/05/30/99bec6cc787188da3751f87718b3f54e.jpg, createdBy=86442053325, createdName=133****4869, createdTime=Thu Sep 14 18:18:35 CST 2017, time=2017-09-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=243975, encodeId=c1322439e5eb, content=这篇文章得仔细拜读.从中学习实验设计.从中能不能找出新的研究方向!, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=24362139065, createdName=1881fe7befm, createdTime=Thu Sep 14 16:18:21 CST 2017, time=2017-09-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=243899, encodeId=80d72438995e, content=运动包治百病, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/09/07/a9772c74ffd6edc03a7f9af07b4747f6.jpg, createdBy=b3722138742, createdName=sunfeifeiyang, createdTime=Thu Sep 14 11:37:07 CST 2017, time=2017-09-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=243795, encodeId=6f8d243e9576, content=学习.谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyhb9xDeHojCicsdRdyC3XXdGk2ib9yLypZuHN06WeW4HO8WN0GGrgEfvnTX8gsckof05GHOU5OM4Mvx/0, createdBy=9cee1982656, createdName=执着追梦, createdTime=Thu Sep 14 06:56:54 CST 2017, time=2017-09-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=243746, encodeId=a6e8243e46c2, content=这个关于临床的设计构想可以借鉴.谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/09/03/4d0fbed0ef4c156dae0e75d85c337b77.jpg, createdBy=074d2111966, createdName=138****9420, createdTime=Thu Sep 14 05:51:26 CST 2017, time=2017-09-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=243737, encodeId=7d61243e3745, content=学习了.谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ad4c106013, createdName=Drhzm308, createdTime=Thu Sep 14 03:53:29 CST 2017, time=2017-09-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=243714, encodeId=414b243e147a, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3da1990174, createdName=yfjms, createdTime=Thu Sep 14 00:13:47 CST 2017, time=2017-09-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=243682, encodeId=27942436821c, content=美国还将运动纳入了乳腺癌的标准治疗指南中.建议乳腺癌患者每周进行150分钟左右的中等强度锻炼., beContent=null, objectType=article, channel=null, level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Pw2csslt7CukWiabqiblnQAXaDEiaxhu025c3P0XshccTrbvGWBjKvnHIxbK3vqa80P7WGIFuicCFet97TicrNKpgB3TdabxP1vMh/0, createdBy=28851960965, createdName=榄枷檬, createdTime=Wed Sep 13 23:26:58 CST 2017, time=2017-09-13, status=1, ipAttribution=)]
    2017-09-14 138****9420

    这个关于临床的设计构想可以借鉴.谢谢分享

    0

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    2017-09-14 Drhzm308

    学习了.谢谢

    0

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    2017-09-14 yfjms

    学习了

    0

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    2017-09-13 榄枷檬

    美国还将运动纳入了乳腺癌的标准治疗指南中.建议乳腺癌患者每周进行150分钟左右的中等强度锻炼.

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