Cancer Cell Int:通过重新激活EGFR/PI3K/AKT信号,SCD1有助于EGFR靶向治疗肺癌

2019-04-28 不详 网络

癌细胞的特征在于脂质生物合成的异常活化,通过硬脂酰-CoA去饱和酶(SCD)产生饱和脂肪酸和单不饱和脂肪酸,用于调节代谢和信号传导。 SCD1过度表达在肺癌中作为致癌基因发挥作用,并预测不佳的临床结果。本研究旨在探讨体外和体内基于EGFR抑制剂(吉非替尼)的肺癌抗肿瘤治疗对SCD1的抑制作用。进行CCK-8测定以确定细胞活力。通过qPCR检测SCD1 mRNA水平。通过蛋白质印迹评估蛋白质水平。通

癌细胞的特征在于脂质生物合成的异常活化,通过硬脂酰-CoA去饱和酶(SCD)产生饱和脂肪酸和单不饱和脂肪酸,用于调节代谢和信号传导。 SCD1过度表达在肺癌中作为致癌基因发挥作用,并预测不佳的临床结果。本研究旨在探讨体外和体内基于EGFR抑制剂(吉非替尼)的肺癌抗肿瘤治疗对SCD1的抑制作用。

进行CCK-8测定以确定细胞活力。通过qPCR检测SCD1 mRNA水平。通过蛋白质印迹评估蛋白质水平。通过免疫荧光测定E-钙粘蛋白和N-钙粘蛋白水平。通过流式细胞术进行细胞凋亡检测。通过transwell测定评估细胞迁移或侵袭。通过皮下注射用pcDNA3.1-SCD1载体或阴性对照转染的A549细胞在裸鼠中计算肿瘤大小和肿瘤体积。通过免疫组织化学检测Ki-67的表达。

结果显示,在肺癌细胞系中观察到SCD1上调的表达。过表达SCD1的细胞对于A549和H1573细胞系中的吉非替尼具有高IC50值。过表达SCD1可抑制吉非替尼诱导的细胞凋亡,降低细胞活力,降低迁移和侵袭能力,而这些作用则被A939572抵消。在机制上,SCD1促进两种细胞系中增殖和转移相关的EGFR/PI3K/AKT信号传导的激活,并上调上皮细胞向间充质细胞转变(EMT)表型,其通过SCD1抑制而恢复。此外,尽管EGFR抑制,体内SCD1的过表达通过激活肿瘤组织中的EGFR/PI3K/AKT信号传导显着促进肿瘤生长,但A939572处理限制了SCD1诱导的肿瘤进展并抑制了体内癌细胞的EMT表型。

总之,这些发现表明,靶向EGFR治疗肺癌需要抑制致癌基因SCD1。

原始出处:

She K, Fang S, et al., SCD1 is required for EGFR-targeting cancer therapy of lung cancer via re-activation of EGFR/PI3K/AKT signals. Cancer Cell Int. 2019 Apr 18;19:103. doi: 10.1186/s12935-019-0809-y. eCollection 2019.





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    2020-02-28 xfpan20
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    2019-11-23 lidong40
  4. 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createdName=xfpan20, createdTime=Fri Feb 28 13:07:00 CST 2020, time=2020-02-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2024155, encodeId=e3352024155a0, content=<a href='/topic/show?id=bbba14239f5' target=_blank style='color:#2F92EE;'>#PI3K/AKT#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14239, encryptionId=bbba14239f5, topicName=PI3K/AKT)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6da1120, createdName=lidong40, createdTime=Sat Nov 23 00:07:00 CST 2019, time=2019-11-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1961534, encodeId=2686196153456, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, 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createdBy=7bb22500091, createdName=ms1292405679162969, createdTime=Tue Apr 30 06:07:00 CST 2019, time=2019-04-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1515388, encodeId=133c15153881b, content=<a href='/topic/show?id=2de3159e3d1' target=_blank style='color:#2F92EE;'>#SCD#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15973, encryptionId=2de3159e3d1, topicName=SCD)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3f5d10780905, createdName=12498b08m93暂无昵称, createdTime=Tue Apr 30 06:07:00 CST 2019, time=2019-04-30, status=1, ipAttribution=)]
    2019-05-18 维他命
  5. 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createdBy=7bb22500091, createdName=ms1292405679162969, createdTime=Tue Apr 30 06:07:00 CST 2019, time=2019-04-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1515388, encodeId=133c15153881b, content=<a href='/topic/show?id=2de3159e3d1' target=_blank style='color:#2F92EE;'>#SCD#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15973, encryptionId=2de3159e3d1, topicName=SCD)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3f5d10780905, createdName=12498b08m93暂无昵称, createdTime=Tue Apr 30 06:07:00 CST 2019, time=2019-04-30, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=1814625, encodeId=9dd0181462516, content=<a href='/topic/show?id=f8f795864d9' target=_blank style='color:#2F92EE;'>#重新激活#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=95864, encryptionId=f8f795864d9, topicName=重新激活)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c737344, createdName=lg.zhao, createdTime=Tue Nov 26 04:07:00 CST 2019, time=2019-11-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1656183, encodeId=bc8f165618379, content=<a href='/topic/show?id=f4782246ec' target=_blank style='color:#2F92EE;'>#Akt#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2246, encryptionId=f4782246ec, topicName=Akt)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b8c724776724, 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level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4016, encryptionId=517a4016ac, topicName=cancer cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=96f62500201, createdName=12498e67m28暂无昵称, createdTime=Sat Dec 28 01:07:00 CST 2019, time=2019-12-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1789042, encodeId=bf971e890421e, content=<a href='/topic/show?id=e05d14241ae' target=_blank style='color:#2F92EE;'>#PI3K/Akt信号#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14241, encryptionId=e05d14241ae, topicName=PI3K/Akt信号)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=80ca273, createdName=fanweitanzhen, createdTime=Tue Sep 17 17:07:00 CST 2019, time=2019-09-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=366823, encodeId=056436682320, 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  7. 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    2019-05-26 zwjnj2

    努力学习天天学习认真的学习

    0

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