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JCEM：新型AMPK激活/mTOR拮抗剂抑制甲状腺癌生长

2015-05-27 沐晴 MedSci原创

甲状腺癌自噬AMPKmTOR
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活化的AMPK是调节细胞内能量稳态的关键调节因子，研究认为，AMPK可通过抑制mTOR/p70S6K信号途径，抑制肿瘤细胞的生长。激活AMPK的药物，如二甲双胍和AICAR，在体内和体外实验中，都证明可以抑制甲状腺癌细胞的生长。<span lang="EN-US" style="mso-bidi-font-size:10.5pt;font-family:Frutiger-Roman; mso-b

活化的AMPK是调节细胞内能量稳态的关键调节因子，研究认为，AMPK可通过抑制mTOR/p70S6K信号途径，抑制肿瘤细胞的生长。激活AMPK的药物，如二甲双胍和AICAR，在体内和体外实验中，都证明可以抑制甲状腺癌细胞的生长。OSU-53是近来研发的AMPK激活剂，体内和体外实验研究证明，OSU-53可以抑制侵袭性乳腺癌细胞的生长。

近来，有研究试图通过体外细胞研究，证明OSU-53对甲状腺癌细胞的治疗作用。研究者通过选择性基因敲除AMPK，分别检测OSU-53对甲状腺癌细胞生长、致癌信号系统、凋亡、自噬的影响。结果显示：OSU-53可以抑制体外7种甲状腺癌细胞的生长，同时激活AMPK。存在RAS或者BRAF突变的细胞系，与缺乏抑癌基因和RET/PTC1突变相比，对于OSU-53治疗更敏感，这证明OSU-53是非常强的激活AMPK，抑制mTOR信号系统，同时激活细胞自噬的药物。在选择性的敲除AMPK后，并没有观察到甲状腺癌细胞可以免于OSU-53的“杀害”。研究者发现，OSU-53还可以通过直接抑制mTOR信号途径抑制甲状腺癌细胞的生长。此外，激活RAS或者BRAF突变，可以提高细胞的自噬水平。

最终，研究者得出结论，OSU-53是一种新型的激活AMPK/拮抗mTOR的抗癌药物，可以有效的抑制多种甲状腺癌的生长，而且，在存在RAS或者BRAF突变的细胞系中作用最强。

原始出处：


Plews RL, Mohd Yusof A, Wang C, et
al.A Novel Dual AMPK Activator/mTOR Inhibitor Inhibits Thyroid Cancer Cell Growth. J Clin Endocrinol Metab. 2015 May;100(5):E748-56. doi:10.1210

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    2016-03-11 smallant2015

    #JCEM#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1777518, encodeId=4d5c1e77518f3, content=<a href='/topic/show?id=eb9610265ed' target=_blank style='color:#2F92EE;'>#JCEM#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, 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=Fri Mar 11 05:55:00 CST 2016, time=2016-03-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2062900, encodeId=9804206290020, content=<a href='/topic/show?id=14fb10264d7' target=_blank style='color:#2F92EE;'>#JCE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10264, encryptionId=14fb10264d7, topicName=JCE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e656479, createdName=achengzhao, createdTime=Sun Sep 13 06:55:00 CST 2015, time=2015-09-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=25597, encodeId=c6492559e36, content=看看, beContent=null, objectType=article, channel=null, level=null, likeNumber=135, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ee0d1618732, createdName=huaxipanxing, createdTime=Sun May 31 21:22:00 CST 2015, time=2015-05-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=25350, encodeId=5c2025350d7, content=转化吧, beContent=null, objectType=article, channel=null, level=null, likeNumber=160, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=jasonuclear, createdTime=Sat May 30 01:10:00 CST 2015, time=2015-05-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1511629, encodeId=3ba6151162965, content=<a href='/topic/show?id=90d75628960' target=_blank style='color:#2F92EE;'>#拮抗剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56289, encryptionId=90d75628960, topicName=拮抗剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=474c10379153, createdName=ms5236388012055669, createdTime=Fri May 29 12:55:00 CST 2015, time=2015-05-29, status=1, ipAttribution=)]
    2015-09-13 achengzhao

    #JCE#

    0

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    2015-05-31 huaxipanxing

    看看

    0

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    2015-05-30 jasonuclear

    转化吧

    0

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    2015-05-29 ms5236388012055669

    #拮抗剂#

    0

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