Cell Death Dis:自噬抑制可增强紫杉醇类似物Alteronol的黑色素瘤细胞上皮-间质转化进程

2020-04-18 QQY MedSci原创

黑色素瘤是由产生色素的黑色素细胞癌变引起的,是一种最具有侵略性的恶性皮肤癌,在所有与皮肤癌有关的死亡中占比高达80-85%,每年约有100,000死亡病例。

黑色素瘤是由产生色素的黑色素细胞癌变引起的,是一种最具有侵略性的恶性皮肤癌,在所有与皮肤癌有关的死亡中占比高达80-85%,每年约有100,000死亡病例。

尽管当前的黑色素瘤疗法包括手术、化疗及生物疗法等方法,但这些疗法的效果仍非常有限,且常引起不良的副作用、耐药性的产生及疾病的复发。因此,进一步开发用于恶性黑色素瘤治疗的新型有效的治疗剂迫在眉睫。

紫杉醇是一种通过微生物菌株从紫杉树皮中分离出来的有效的抗肿瘤药物,被用作各类癌症的一线化疗药物。

Alteronol是一种与紫杉醇具有相似结构的新型化合物,既往研究表明,Alteronol可以通过诱导细胞凋亡、细胞周期停滞以及抑制细胞侵袭/迁移作用来发挥抗肿瘤作用。

然而,Alteronol能否诱导细胞自噬发生,以及其抗癌作用与黑色素瘤自噬之间的关系尚不清楚。

在该研究中,研究人员发现Alteronol不仅能够诱导激活抗增殖反应及凋亡的产生,而且还能够诱导A375及UACC62细胞自噬反应。此外,Alteronol可以通过阻止上皮-间质转化(EMT)进程,进而抑制A375及UACC62细胞侵袭和迁移能力。

内外源阻断细胞自噬的发生均能够增强Alteronol的诱导凋亡能力及抗EMT作用。

机制研究发现,Alteronol可以显著抑制Akt/mTOR以及TGFβ/Smad3信号通路,与自噬抑制剂3-MA联合治疗可以进一步增强这些作用。

以上的研究结果表明,Alteronol可以通过抑制Akt/mTOR信号通路诱导黑素瘤细胞的细胞保护性自噬,同时通过抑制TGF-β/ Smad3信号通路减弱细胞凋亡反应并促进黑素瘤细胞的EMT进程。

Alteronol与自噬抑制剂3-MA的联合用药可能是治疗黑色素瘤的潜在方法,其不仅可以显著抑制肿瘤的生长,且可以作为抗转移剂来抑制肿瘤的侵袭及迁移。

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    2020-05-16 sunylz
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    2020-07-22 docwu2019
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  4. 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createdName=docwu2019, createdTime=Wed Jul 22 00:15:58 CST 2020, time=2020-07-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2013297, encodeId=32bb201329eca, content=<a href='/topic/show?id=7d69598468' target=_blank style='color:#2F92EE;'>#Dis#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5984, encryptionId=7d69598468, topicName=Dis)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c689267, createdName=cmj8wellington, createdTime=Thu Jun 18 17:15:58 CST 2020, time=2020-06-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1861378, encodeId=1f6118613e8ae, content=<a href='/topic/show?id=401a23e102' target=_blank style='color:#2F92EE;'>#ALT#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2371, encryptionId=401a23e102, topicName=ALT)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ccbd84, createdName=shizhenshan, createdTime=Wed Jan 06 05:15:58 CST 2021, time=2021-01-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1779730, encodeId=701e1e7973024, content=<a href='/topic/show?id=00d523e81f' target=_blank style='color:#2F92EE;'>#Alteronol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2378, encryptionId=00d523e81f, topicName=Alteronol)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8942242, createdName=jj000001, createdTime=Tue Mar 09 02:15:58 CST 2021, time=2021-03-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1871679, encodeId=b4d218e167910, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Tue Jan 26 23:15:58 CST 2021, time=2021-01-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1966920, encodeId=1f021966920c8, content=<a href='/topic/show?id=408a103334eb' target=_blank style='color:#2F92EE;'>#黑色素瘤细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103334, encryptionId=408a103334eb, topicName=黑色素瘤细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f5e185, createdName=zlawrance, createdTime=Thu Sep 17 11:15:58 CST 2020, time=2020-09-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1531584, encodeId=288a15315841e, content=<a href='/topic/show?id=770e5e9457' target=_blank style='color:#2F92EE;'>#Death#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, 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=Mon Apr 20 05:15:58 CST 2020, time=2020-04-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1559003, encodeId=efbd1559003f2, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Mon Apr 20 05:15:58 CST 2020, time=2020-04-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1565012, encodeId=15b21565012d6, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Mon Apr 20 05:15:58 CST 2020, time=2020-04-20, status=1, ipAttribution=)]
    2021-01-06 shizhenshan
  5. [GetPortalCommentsPageByObjectIdResponse(id=1680663, encodeId=c70e1680663ac, content=<a href='/topic/show?id=9e5c86e0712' target=_blank style='color:#2F92EE;'>#色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86707, encryptionId=9e5c86e0712, topicName=色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=343027846633, createdName=sunylz, createdTime=Sat May 16 22:15:58 CST 2020, time=2020-05-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1961973, encodeId=9dc319619e377, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, 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encryptionId=401a23e102, topicName=ALT)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ccbd84, createdName=shizhenshan, createdTime=Wed Jan 06 05:15:58 CST 2021, time=2021-01-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1779730, encodeId=701e1e7973024, content=<a href='/topic/show?id=00d523e81f' target=_blank style='color:#2F92EE;'>#Alteronol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2378, encryptionId=00d523e81f, topicName=Alteronol)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8942242, createdName=jj000001, createdTime=Tue Mar 09 02:15:58 CST 2021, time=2021-03-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1871679, encodeId=b4d218e167910, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Tue Jan 26 23:15:58 CST 2021, time=2021-01-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1966920, encodeId=1f021966920c8, content=<a href='/topic/show?id=408a103334eb' target=_blank style='color:#2F92EE;'>#黑色素瘤细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103334, encryptionId=408a103334eb, topicName=黑色素瘤细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f5e185, createdName=zlawrance, createdTime=Thu Sep 17 11:15:58 CST 2020, time=2020-09-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1531584, encodeId=288a15315841e, content=<a href='/topic/show?id=770e5e9457' target=_blank style='color:#2F92EE;'>#Death#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, 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=Mon Apr 20 05:15:58 CST 2020, time=2020-04-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1559003, encodeId=efbd1559003f2, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Mon Apr 20 05:15:58 CST 2020, time=2020-04-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1565012, encodeId=15b21565012d6, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Mon Apr 20 05:15:58 CST 2020, time=2020-04-20, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=1680663, encodeId=c70e1680663ac, content=<a href='/topic/show?id=9e5c86e0712' target=_blank style='color:#2F92EE;'>#色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86707, encryptionId=9e5c86e0712, topicName=色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=343027846633, createdName=sunylz, createdTime=Sat May 16 22:15:58 CST 2020, time=2020-05-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1961973, encodeId=9dc319619e377, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, 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encryptionId=401a23e102, topicName=ALT)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ccbd84, createdName=shizhenshan, createdTime=Wed Jan 06 05:15:58 CST 2021, time=2021-01-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1779730, encodeId=701e1e7973024, content=<a href='/topic/show?id=00d523e81f' target=_blank style='color:#2F92EE;'>#Alteronol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2378, encryptionId=00d523e81f, topicName=Alteronol)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8942242, createdName=jj000001, createdTime=Tue Mar 09 02:15:58 CST 2021, time=2021-03-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1871679, encodeId=b4d218e167910, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Tue Jan 26 23:15:58 CST 2021, time=2021-01-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1966920, encodeId=1f021966920c8, content=<a href='/topic/show?id=408a103334eb' target=_blank style='color:#2F92EE;'>#黑色素瘤细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103334, encryptionId=408a103334eb, topicName=黑色素瘤细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f5e185, createdName=zlawrance, createdTime=Thu Sep 17 11:15:58 CST 2020, time=2020-09-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1531584, encodeId=288a15315841e, content=<a 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time=2020-04-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1565012, encodeId=15b21565012d6, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Mon Apr 20 05:15:58 CST 2020, time=2020-04-20, status=1, ipAttribution=)]
  7. [GetPortalCommentsPageByObjectIdResponse(id=1680663, encodeId=c70e1680663ac, content=<a href='/topic/show?id=9e5c86e0712' target=_blank style='color:#2F92EE;'>#色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86707, encryptionId=9e5c86e0712, topicName=色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=343027846633, createdName=sunylz, createdTime=Sat May 16 22:15:58 CST 2020, time=2020-05-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1961973, encodeId=9dc319619e377, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, 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  8. 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time=2020-04-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1565012, encodeId=15b21565012d6, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Mon Apr 20 05:15:58 CST 2020, time=2020-04-20, status=1, ipAttribution=)]
    2020-04-20 cy0328
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