Cell Death Dis:小分子化合物AH057与SGI-1027联合抑制宫颈癌细胞的发生发展

2020-09-09 QQY MedSci原创

宫颈癌(CC)是第三大最常见的妇科癌症,在全世界女性中具有高发病率和高死亡率的特点。超过85%的CC发病率和死亡率主要发生在诊断仍不完善的发展中国家。

宫颈癌(CC)是第三大最常见的妇科癌症,在全世界女性中具有高发病率和高死亡率的特点。超过85%的CC发病率和死亡率主要发生在诊断仍不完善的发展中国家。

尽管通过手术、放疗和化疗等治疗手段在CC的治疗方面上取得了重大的进展,但由于肿瘤的复发和转移,晚期CC患者的预后仍然很差。因此,开发更有效更具特异性的CC治疗策略迫在眉睫。

该研究通过模拟筛选SPECS数据库,鉴定了多种候选的新型JAK抑制剂,并评估这些候选药物的抗肿瘤效果尤其是对CC细胞系的作用。 AH057是公认最佳的JAK抑制剂,其可以通过直接抑制JAK1/2激酶的活性来有效的阻断JAK/STAT信号通路,最终导致细胞增殖和侵袭作用的抑制、细胞凋亡的增加、细胞周期的停滞以及抑制肿瘤的发生发展。

研究人员进一步通过筛选Selleck化学文库,筛选了与AH057具有最高协同作用的化合物DNMT1抑制剂SGI-1027。AH057与SGI-1027联合使用可以通过作用于受JAK1/2和DNMT1双重控制的一组下游效应分子,来显著增加细胞凋亡反应和细胞周期的停滞,从而有效地协同抑制CC细胞的增殖。

总而言之,以上研究结果显示双重靶向JAK1/2和DNMT1对于宫颈癌治疗的临床证据,也为临床上的药物联合治疗CC和其他恶性肿瘤患者的疗效和安全性分析提供了支持。


原始出处:

She, S., Zhao, Y., Kang, B. et al. Combined inhibition of JAK1/2 and DNMT1 by newly identified small-molecule compounds synergistically suppresses the survival and proliferation of cervical cancer cells. Cell Death Dis 11, 724 (07 September 2020).

 

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encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=395f25, createdName=爆笑小医, createdTime=Mon Nov 23 04:26:51 CST 2020, time=2020-11-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2013468, encodeId=ccf92013468cc, content=<a href='/topic/show?id=7d69598468' target=_blank style='color:#2F92EE;'>#Dis#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5984, encryptionId=7d69598468, topicName=Dis)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c689267, createdName=cmj8wellington, createdTime=Tue Sep 22 00:26:51 CST 2020, time=2020-09-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1914707, encodeId=11581914e077c, content=<a href='/topic/show?id=84d7469559b' target=_blank style='color:#2F92EE;'>#小分子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=46955, encryptionId=84d7469559b, topicName=小分子)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6105386, createdName=宋威, createdTime=Sat Aug 07 07:26:51 CST 2021, time=2021-08-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=885070, encodeId=60358850e0f7, content=阅读谢谢分享谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2017/04/21/72142930668371951a41ef4ea4b233e6.jpg, createdBy=dcbc1715228, createdName=刘煜, createdTime=Mon Sep 14 06:39:08 CST 2020, time=2020-09-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1252727, encodeId=0abf1252e27c4, 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=20, 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=Thu Sep 10 15:26:51 CST 2020, time=2020-09-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1408242, encodeId=f28c14082426d, content=<a href='/topic/show?id=92194628826' target=_blank style='color:#2F92EE;'>#宫颈#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=46288, encryptionId=92194628826, topicName=宫颈)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=11102737131, createdName=一闲, createdTime=Thu Sep 10 15:26:51 CST 2020, time=2020-09-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1531665, encodeId=af68153166541, content=<a href='/topic/show?id=770e5e9457' target=_blank style='color:#2F92EE;'>#Death#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5794, encryptionId=770e5e9457, topicName=Death)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=32e312278742, createdName=cy0328, createdTime=Thu Sep 10 15:26:51 CST 2020, time=2020-09-10, status=1, ipAttribution=)]
    2020-11-23 爆笑小医
  5. 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encodeId=af68153166541, content=<a href='/topic/show?id=770e5e9457' target=_blank style='color:#2F92EE;'>#Death#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5794, encryptionId=770e5e9457, topicName=Death)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=32e312278742, createdName=cy0328, createdTime=Thu Sep 10 15:26:51 CST 2020, time=2020-09-10, status=1, ipAttribution=)]
  6. 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encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=395f25, createdName=爆笑小医, createdTime=Mon Nov 23 04:26:51 CST 2020, time=2020-11-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2013468, encodeId=ccf92013468cc, content=<a href='/topic/show?id=7d69598468' target=_blank style='color:#2F92EE;'>#Dis#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5984, encryptionId=7d69598468, topicName=Dis)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c689267, createdName=cmj8wellington, createdTime=Tue Sep 22 00:26:51 CST 2020, time=2020-09-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1914707, encodeId=11581914e077c, content=<a href='/topic/show?id=84d7469559b' target=_blank style='color:#2F92EE;'>#小分子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=46955, encryptionId=84d7469559b, topicName=小分子)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6105386, createdName=宋威, createdTime=Sat Aug 07 07:26:51 CST 2021, time=2021-08-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=885070, encodeId=60358850e0f7, content=阅读谢谢分享谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2017/04/21/72142930668371951a41ef4ea4b233e6.jpg, createdBy=dcbc1715228, createdName=刘煜, createdTime=Mon Sep 14 06:39:08 CST 2020, time=2020-09-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1252727, encodeId=0abf1252e27c4, 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=20, 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=Thu Sep 10 15:26:51 CST 2020, time=2020-09-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1408242, encodeId=f28c14082426d, content=<a href='/topic/show?id=92194628826' target=_blank style='color:#2F92EE;'>#宫颈#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=46288, encryptionId=92194628826, topicName=宫颈)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=11102737131, createdName=一闲, createdTime=Thu Sep 10 15:26:51 CST 2020, time=2020-09-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1531665, encodeId=af68153166541, content=<a href='/topic/show?id=770e5e9457' target=_blank style='color:#2F92EE;'>#Death#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5794, encryptionId=770e5e9457, topicName=Death)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=32e312278742, createdName=cy0328, createdTime=Thu Sep 10 15:26:51 CST 2020, time=2020-09-10, status=1, ipAttribution=)]
    2021-08-07 宋威
  7. 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encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=395f25, createdName=爆笑小医, createdTime=Mon Nov 23 04:26:51 CST 2020, time=2020-11-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2013468, encodeId=ccf92013468cc, content=<a href='/topic/show?id=7d69598468' target=_blank style='color:#2F92EE;'>#Dis#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5984, encryptionId=7d69598468, topicName=Dis)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c689267, createdName=cmj8wellington, createdTime=Tue Sep 22 00:26:51 CST 2020, time=2020-09-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1914707, encodeId=11581914e077c, content=<a href='/topic/show?id=84d7469559b' target=_blank style='color:#2F92EE;'>#小分子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=46955, encryptionId=84d7469559b, topicName=小分子)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6105386, createdName=宋威, createdTime=Sat Aug 07 07:26:51 CST 2021, time=2021-08-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=885070, encodeId=60358850e0f7, content=阅读谢谢分享谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2017/04/21/72142930668371951a41ef4ea4b233e6.jpg, createdBy=dcbc1715228, createdName=刘煜, createdTime=Mon Sep 14 06:39:08 CST 2020, time=2020-09-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1252727, encodeId=0abf1252e27c4, 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=20, 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=Thu Sep 10 15:26:51 CST 2020, time=2020-09-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1408242, encodeId=f28c14082426d, content=<a href='/topic/show?id=92194628826' target=_blank style='color:#2F92EE;'>#宫颈#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=46288, encryptionId=92194628826, topicName=宫颈)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=11102737131, createdName=一闲, createdTime=Thu Sep 10 15:26:51 CST 2020, time=2020-09-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1531665, encodeId=af68153166541, content=<a href='/topic/show?id=770e5e9457' target=_blank style='color:#2F92EE;'>#Death#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5794, encryptionId=770e5e9457, topicName=Death)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=32e312278742, createdName=cy0328, createdTime=Thu Sep 10 15:26:51 CST 2020, time=2020-09-10, status=1, ipAttribution=)]
    2020-09-14 刘煜

    阅读谢谢分享谢谢

    0

  8. 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    2020-09-10 yxch36
  9. 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    2020-09-10 一闲
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    2020-09-10 cy0328

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