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JCEM：二甲双胍的抗肿瘤作用

2015-04-20 沐晴 译 MedSci原创

二甲双胍肿瘤
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二甲双胍是广泛认可的2型糖尿病一线治疗药物，近来研究发现，它还有潜在的抗肿瘤作用。无论是在动物，还是人体试验，都发现二甲双胍可以通过AMPK依赖的通路抑制哺乳动物类雷帕霉素靶蛋白信号通路，抑制肿瘤细胞的生长。早期的观察性研究发现，在使用二甲双胍治疗的糖尿病患者中，癌症的发生风险降低，已存在癌症的进展被阻止。而且，多项研究表明，二甲双胍可以影响NF- kB的活性。NF- kB是一种转录因子，可以激活

二甲双胍是广泛认可的2型糖尿病一线治疗药物，近来研究发现，它还有潜在的抗肿瘤作用。无论是在动物，还是人体试验，都发现二甲双胍可以通过AMPK依赖的通路抑制哺乳动物类雷帕霉素靶蛋白信号通路，抑制肿瘤细胞的生长。早期的观察性研究发现，在使用二甲双胍治疗的糖尿病患者中，癌症的发生风险降低，已存在癌症的进展被阻止。

而且，多项研究表明，二甲双胍可以影响NF- kB的活性。NF- kB是一种转录因子，可以激活许多种癌症，调节与细胞增殖、存活、侵袭有关的多种基因。而CXCL8是NF- kB信号系统下游的，与甲状腺癌的生长和进展相关的一个关键的介导因子，在体动物甲状腺癌实验发现，以CXCL8为靶向的治疗可以延长生存期，减少肿瘤的转移。

近来，有研究发现，在人甲状腺癌细胞的原代培养中，二甲双胍可以逆转TNF-a诱导的CXCL8的分泌，二甲双胍表现出间接的抗肿瘤效应。研究者使用TNF-a单独或/结合二甲双胍(0.01, 0.1, 1, 2.5, 5, and 10mM)浓度组，刺激正常甲状腺细胞，甲状腺乳头状癌细胞，及甲状腺癌细胞系（TPC-1和BCPAP），将细胞培养24小时后，检测细胞上清液中CXCL8的水平。

结果显示：在正常甲状腺细胞(ANOVA: F=42.04; P<0 .0001)和乳头状甲状腺癌细胞(ANOVA: F = 21.691; P <0 .0001)中，二甲双胍显著的抑制TNF-a诱导的CXCL8的分泌，并呈现浓度依赖性，但是在TPC-1 和 BCPAP细胞系中并没有得出此结论。

因此，在原代培养的正常甲状腺癌细胞和已分化的甲状腺癌细胞中，至少是在最常见的侵袭性最差的甲状腺癌表型中，二甲双胍可以抑制TNF-a诱导的CXCL8的分泌。甲状腺组织中中性粒细胞的募集是非常关紧的促代谢因素，在暴露于TNF-a刺激中的肿瘤细胞和大多数正常甲状腺细胞中，它取决于细胞分泌的CXCL8的数量。固此研究发现的二甲双胍对TNF-a诱导的CXCL8分泌的抑制作用，可以认为是二甲双胍的一个间接的抗肿瘤效应。

原始出处：

Rotondi M, Coperchini F, Pignatti P,et al.Metformin reverts the secretion of CXCL8 induced by TNF-α in primary cultures of human thyroid cells: an additional indirect anti-tumor effect of the drug. J Clin Endocrinol Metab. 2015 Mar;100(3):E427-32. doi: 10.1210/jc.2014-3045. Epub 2015 Jan 15

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    2015-10-26 smallant2015

    #JCEM#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1777511, encodeId=2a3a1e77511f7, content=<a href='/topic/show?id=eb9610265ed' target=_blank style='color:#2F92EE;'>#JCEM#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10265, encryptionId=eb9610265ed, topicName=JCEM)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2a4439169927, createdName=smallant2015, createdTime=Mon Oct 26 12:13:00 CST 2015, time=2015-10-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2062893, encodeId=03992062893d2, content=<a href='/topic/show?id=14fb10264d7' target=_blank style='color:#2F92EE;'>#JCE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10264, encryptionId=14fb10264d7, topicName=JCE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e656479, createdName=achengzhao, createdTime=Thu Sep 10 15:13:00 CST 2015, time=2015-09-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=33618, encodeId=9b36336188b, content=挺好, beContent=null, objectType=article, channel=null, level=null, likeNumber=154, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=78351636049, createdName=shuaijing1986, createdTime=Tue Jul 28 05:32:00 CST 2015, time=2015-07-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=21532, encodeId=edef215328f, content=等待临床试验结果, beContent=null, objectType=article, channel=null, level=null, likeNumber=97, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8b26101142, createdName=leaderbilly, createdTime=Tue Apr 21 08:29:00 CST 2015, time=2015-04-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=21504, encodeId=0ca4215040e, content=不可信, beContent=null, objectType=article, channel=null, level=null, likeNumber=148, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=cspcsp, createdTime=Mon Apr 20 22:57:00 CST 2015, time=2015-04-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=21505, encodeId=a3af215056f, content=伟哥的翻版, beContent=null, objectType=article, channel=null, level=null, likeNumber=187, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=cspcsp, createdTime=Mon Apr 20 22:57:00 CST 2015, time=2015-04-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=21469, encodeId=12e421469ae, content=这是基础研究，不等于临床有效, beContent=null, objectType=article, channel=null, level=null, likeNumber=108, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=58.33.143.**, createdTime=Mon Apr 20 21:20:00 CST 2015, time=2015-04-20, status=1, ipAttribution=)]
    2015-09-10 achengzhao

    #JCE#

    0

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    2015-07-28 shuaijing1986

    挺好

    0

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    2015-04-21 leaderbilly

    等待临床试验结果

    0

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    2015-04-20 cspcsp

    不可信

    0

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    2015-04-20 cspcsp

    伟哥的翻版

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1777511, encodeId=2a3a1e77511f7, content=<a href='/topic/show?id=eb9610265ed' target=_blank style='color:#2F92EE;'>#JCEM#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10265, encryptionId=eb9610265ed, topicName=JCEM)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2a4439169927, createdName=smallant2015, createdTime=Mon Oct 26 12:13:00 CST 2015, time=2015-10-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2062893, encodeId=03992062893d2, content=<a href='/topic/show?id=14fb10264d7' target=_blank style='color:#2F92EE;'>#JCE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10264, encryptionId=14fb10264d7, topicName=JCE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e656479, createdName=achengzhao, createdTime=Thu Sep 10 15:13:00 CST 2015, time=2015-09-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=33618, encodeId=9b36336188b, content=挺好, beContent=null, objectType=article, channel=null, level=null, likeNumber=154, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=78351636049, createdName=shuaijing1986, createdTime=Tue Jul 28 05:32:00 CST 2015, time=2015-07-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=21532, encodeId=edef215328f, content=等待临床试验结果, beContent=null, objectType=article, channel=null, level=null, likeNumber=97, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8b26101142, createdName=leaderbilly, createdTime=Tue Apr 21 08:29:00 CST 2015, time=2015-04-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=21504, encodeId=0ca4215040e, content=不可信, beContent=null, objectType=article, channel=null, level=null, likeNumber=148, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=cspcsp, createdTime=Mon Apr 20 22:57:00 CST 2015, time=2015-04-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=21505, encodeId=a3af215056f, content=伟哥的翻版, beContent=null, objectType=article, channel=null, level=null, likeNumber=187, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=cspcsp, createdTime=Mon Apr 20 22:57:00 CST 2015, time=2015-04-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=21469, encodeId=12e421469ae, content=这是基础研究，不等于临床有效, beContent=null, objectType=article, channel=null, level=null, likeNumber=108, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=58.33.143.**, createdTime=Mon Apr 20 21:20:00 CST 2015, time=2015-04-20, status=1, ipAttribution=)]
    2015-04-20 58.33.143.**

    这是基础研究，不等于临床有效

    0

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