Cell Res：抗肿瘤药物可维持胚胎干细胞的自我更新

2014-09-16 MedSci MedSci原创

激活LIF-STAT通路或抑制TGFb/ERK等促进分化的通路可以有效促进胚胎干细胞的自我更新，并使得胚胎干细胞的体外培养得以实现。8月22日，Cell Research在线发表了谢欣研究组关于胚胎干细胞的自我更新及体细胞重编程的最新研究成果。  中科院上海药物所谢欣研究组发现即使在LIF存在的条件下，小鼠胚胎干细胞还是很容易自发向中内胚层分化，并且分泌VEGF。利用靶向受体型

激活LIF-STAT通路或抑制TGFb/ERK等促进分化的通路可以有效促进胚胎干细胞的自我更新，并使得胚胎干细胞的体外培养得以实现。8月22日，Cell Research在线发表了谢欣研究组关于胚胎干细胞的自我更新及体细胞重编程的最新研究成果。

中科院上海药物所谢欣研究组发现即使在LIF存在的条件下，小鼠胚胎干细胞还是很容易自发向中内胚层分化，并且分泌VEGF。利用靶向受体型络氨酸激酶的抗肿瘤药物舒尼替尼（Sunitinib，Sutent）抑制VEGF受体（VEGFRs）即可有效防止胚胎干细胞的自发分化，并在无LIF和滋养层细胞的条件下促进干细胞自我更新。舒尼替尼也可以促进Oct4一因子诱导的体细胞重编程效率。敲除或利用抗体抑制VEGFR2可以模拟舒尼替尼的作用，促进干细胞自我更新。进一步研究显示缺氧诱导因子HIF1a和内质网应激促进胚胎干细胞分泌VEGF，抑制这两条通路都对干性维持有利。有趣的是LIF也会下调上述通路，提示LIF维持干性的作用不止是激活STAT3。上述研究显示胚胎干细胞存在一条自分泌VEGF并诱导自发分化的通路，利用小分子化合物抑制该通路可以有效维持干细胞的自我更新。

MedSci简评：这一机制是否给靶向药物的前景蒙上阴影。许多靶向药物最终临床效果并不令人满意，虽然短期可以控制肿瘤的生长，但长期却并不改善患者的总生存，是否与肿瘤肿瘤干细胞的生长有关？这是值得今后深入研究的课题

原始出处：

Chen G, Xu X, Zhang L, Fu Y, Wang M, Gu H, Xie X.Blocking autocrine VEGF signaling by sunitinib, an anti-cancer drug, promotes embryonic stem cell self-renewal and somatic cell reprogramming. Cell Res. 2014 Sep;24(9):1121-36

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2014-09-26 zhaozhouchifen

#Cell#

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2014-11-12 xsm926

#自我更新#

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2014-11-03 维他命

#CEL#

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createdBy=7a3710, createdName=lovetcm, createdTime=Tue Sep 16 10:10:00 CST 2014, time=2014-09-16, status=1, ipAttribution=)]
2014-09-18 ailian1202

#胚胎#

27 0
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createdBy=7a3710, createdName=lovetcm, createdTime=Tue Sep 16 10:10:00 CST 2014, time=2014-09-16, status=1, ipAttribution=)]
2014-09-18 zhaojie88

#胚胎干细胞#

26 0
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time=2014-09-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1593664, encodeId=0b6c159366493, content=<a href='/topic/show?id=ff895565586' target=_blank style='color:#2F92EE;'>#抗肿瘤药#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55655, encryptionId=ff895565586, topicName=抗肿瘤药)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=aa5e18156549, createdName=zhu_jun9843, createdTime=Thu Sep 18 01:01:00 CST 2014, time=2014-09-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=11665, encodeId=1e151166518, content=能不能按这个方向申请明年国自然？, beContent=null, objectType=article, channel=null, level=null, likeNumber=126, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Tue Sep 16 10:10:00 CST 2014, time=2014-09-16, status=1, ipAttribution=)]
2014-09-18 smartjoy

#肿瘤药物#

28 0
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2014-09-18 30397608

#肿瘤药#

21 0
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encryptionId=6fcc83e0554, topicName=胚胎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6393434, createdName=ailian1202, createdTime=Thu Sep 18 01:01:00 CST 2014, time=2014-09-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1351203, encodeId=ddd5135120343, content=<a href='/topic/show?id=37b083e182b' target=_blank style='color:#2F92EE;'>#胚胎干细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83718, encryptionId=37b083e182b, topicName=胚胎干细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Thu Sep 18 01:01:00 CST 2014, time=2014-09-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1446745, encodeId=32371446e4574, content=<a href='/topic/show?id=94bd830865e' target=_blank style='color:#2F92EE;'>#肿瘤药物#</a>, beContent=null, objectType=article, 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time=2014-09-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1593664, encodeId=0b6c159366493, content=<a href='/topic/show?id=ff895565586' target=_blank style='color:#2F92EE;'>#抗肿瘤药#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55655, encryptionId=ff895565586, topicName=抗肿瘤药)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=aa5e18156549, createdName=zhu_jun9843, createdTime=Thu Sep 18 01:01:00 CST 2014, time=2014-09-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=11665, encodeId=1e151166518, content=能不能按这个方向申请明年国自然？, beContent=null, objectType=article, channel=null, level=null, likeNumber=126, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Tue Sep 16 10:10:00 CST 2014, time=2014-09-16, status=1, ipAttribution=)]
2014-09-18 zhu_jun9843

#抗肿瘤药#

27 0
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encryptionId=6fcc83e0554, topicName=胚胎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6393434, createdName=ailian1202, createdTime=Thu Sep 18 01:01:00 CST 2014, time=2014-09-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1351203, encodeId=ddd5135120343, content=<a href='/topic/show?id=37b083e182b' target=_blank style='color:#2F92EE;'>#胚胎干细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83718, encryptionId=37b083e182b, topicName=胚胎干细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Thu Sep 18 01:01:00 CST 2014, time=2014-09-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1446745, encodeId=32371446e4574, content=<a href='/topic/show?id=94bd830865e' target=_blank style='color:#2F92EE;'>#肿瘤药物#</a>, beContent=null, objectType=article, 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time=2014-09-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1593664, encodeId=0b6c159366493, content=<a href='/topic/show?id=ff895565586' target=_blank style='color:#2F92EE;'>#抗肿瘤药#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55655, encryptionId=ff895565586, topicName=抗肿瘤药)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=aa5e18156549, createdName=zhu_jun9843, createdTime=Thu Sep 18 01:01:00 CST 2014, time=2014-09-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=11665, encodeId=1e151166518, content=能不能按这个方向申请明年国自然？, beContent=null, objectType=article, channel=null, level=null, likeNumber=126, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Tue Sep 16 10:10:00 CST 2014, time=2014-09-16, status=1, ipAttribution=)]
2014-09-16 lovetcm

能不能按这个方向申请明年国自然？

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