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Cancer Cell：科学家发现利用低剂量药物AZA和DAC可重编程癌细胞

2012-04-02 towersimper 生物谷

阿扎胞苷地西他滨分化
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阿扎胞苷(azacitidine, AZA)结构式，图片来自维基共享资源。 地西他滨(decitabine, DAC)结构式，图片来自维基共享资源。 利用细胞培养物进行实验，来自约翰霍普金斯大学基梅尔癌症研究中心的研究人员发现两种曾经被认为在人癌症治疗中毒性过强的药物的新用途。这两种药物阿扎胞苷(azacitidine, AZA)和地西他滨(decitabine, DAC)是DNA去甲基化


阿扎胞苷(azacitidine, AZA)结构式，图片来自维基共享资源。


地西他滨(decitabine, DAC)结构式，图片来自维基共享资源。

利用细胞培养物进行实验，来自约翰霍普金斯大学基梅尔癌症研究中心的研究人员发现两种曾经被认为在人癌症治疗中毒性过强的药物的新用途。这两种药物阿扎胞苷(azacitidine, AZA)和地西他滨(decitabine, DAC)是DNA去甲基化试剂，通过校正导致癌症产生的DNA甲基化变化来发挥作用。

研究人员说，他们发现这两种药物也能够靶向一小群危险性的能够自我更新的细胞，即癌干细胞(cancer stem cell, 译者注：也常译作肿瘤干细胞)。鉴于癌干细胞逃避大多数抗癌药物治疗并导致肿瘤复发和扩散，所以这项研究有可能让人们开发出一种新的抗癌疗法。相关研究结果于2012年3月20日发表在《细胞》子刊《癌细胞》期刊上。研究人员还说，他们在细胞培养物上的测试结果证实低剂量的AZA和DAC药物在乳腺癌、肺癌和结肠癌上产生抗肿瘤反应。约翰霍普金斯大学基梅尔癌症研究中心副主任和肿瘤学教授Stephen Baylin博士认为，这两种药物可能重新激活阻止癌症生长的基因，从而很快导致癌细胞死亡或DNA损伤。

因为标准高剂量AZA和DAC药物过于毒性，所以很多癌症专家已经放弃用它们来治疗常见性癌症，而且也很少有研究揭示它们可能如何抵抗癌症。Baylin和他的同事Cynthia Zahnow博士因为发现这两种药物低剂量时有益于骨髓增生异常综合症(myelodysplastic syndrome，一种白血病前期疾病)病人，于是便决定对它们进行一番研究。他们在细胞培养物测试中也发现它们低剂量时也有益于一小部分晚期癌症病人。

低剂量药物治疗逆转癌细胞遗传途径，包括那些控制细胞周期的、细胞修复、细胞成熟、细胞分化、免疫细胞相互作用和细胞死亡的基因。尽管在单个肿瘤细胞之间这些影响存在变化，但是科学家总体上发现癌细胞逆转到一种更加正常的状态并且最终死掉。这些结果部分上是由于DNA甲基化发生变化而导致的。Zahnow说，DNA甲基化变化开启某些基因，同时关闭其他一些基因。

研究小组也测试了AZA和DAC药物在一种被认为促进癌症生长和抵抗标准抗癌治疗方法的转移性乳腺癌细胞上的疗效。人们在标准实验室肿瘤模式中很难研究转移瘤细胞(metastatic cell)，这是因为它们往往从原始肿瘤中脱离下来，在血液和淋巴液中到处漂浮。在这项研究中，研究小组重建了转移性癌干细胞环境，允许癌干细胞作为漂浮球体(floating sphere)进行生长。Zahnow说，“这些细胞作为悬浮球体生长得很好，但是当我们用AZA处理它们时，球体的大小和数量发生显著性降低。”

约翰霍普金斯大学Charles Rudin博士领导的一个研究小组于2011年年底在Cancer Discovery期刊上发表的肺癌临床试验结果也表明，这两种药物使得肺癌对标准抗癌药物治疗更加敏感。这意味着它们可能成为组合疗法的一部分而不是单独用来进行治疗，同时它们也可能成为病人个人化治疗的一部分，因为这些病人所患的癌症拥有特异性的表观遗传谱和基因谱(genetic profile)。

doi:10.1016/j.ccr.2011.12.029
PMC:
PMID:

Transient Low Doses of DNA-Demethylating Agents Exert Durable Antitumor Effects on Hematological and Epithelial Tumor Cells

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    2012-04-22 zhaozhouchifen

    #Cell#

    0

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    2013-02-04 维他命

    #CEL#

    0

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    2013-03-15 12498e67m28暂无昵称

    #cancer cell#

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1868472, encodeId=1f1718684e2b8, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Sun Apr 22 02:10:00 CST 2012, time=2012-04-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1958686, encodeId=76b6195868670, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Mon Feb 04 20:10:00 CST 2013, time=2013-02-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1780561, encodeId=e0971e8056149, content=<a href='/topic/show?id=517a4016ac' target=_blank style='color:#2F92EE;'>#cancer cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, 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=Fri Mar 15 01:10:00 CST 2013, time=2013-03-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1802154, encodeId=724018021545c, content=<a href='/topic/show?id=acfae485578' target=_blank style='color:#2F92EE;'>#科学家发现#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74855, encryptionId=acfae485578, topicName=科学家发现)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e572480, createdName=旅苦化文_208, createdTime=Fri Jan 18 00:10:00 CST 2013, time=2013-01-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1714692, encodeId=e5441e1469251, content=<a href='/topic/show?id=021230e312' target=_blank style='color:#2F92EE;'>#AZ#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3073, encryptionId=021230e312, topicName=AZ)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9e5031899089, createdName=12498e5fm22(暂无昵称), createdTime=Fri Oct 26 05:10:00 CST 2012, time=2012-10-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1251856, encodeId=f3a61251856ae, 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=29, 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=Wed Apr 04 11:10:00 CST 2012, time=2012-04-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1480392, encodeId=c04d1480392f5, content=<a href='/topic/show?id=647d2615939' target=_blank style='color:#2F92EE;'>#低剂量#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=26159, encryptionId=647d2615939, topicName=低剂量)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=97b17641126, createdName=ms1292405679162969, createdTime=Wed Apr 04 11:10:00 CST 2012, time=2012-04-04, status=1, ipAttribution=)]
    2013-01-18 旅苦化文_208

    #科学家发现#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1868472, encodeId=1f1718684e2b8, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Sun Apr 22 02:10:00 CST 2012, time=2012-04-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1958686, encodeId=76b6195868670, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Mon Feb 04 20:10:00 CST 2013, time=2013-02-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1780561, encodeId=e0971e8056149, content=<a href='/topic/show?id=517a4016ac' target=_blank style='color:#2F92EE;'>#cancer cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, 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=Fri Mar 15 01:10:00 CST 2013, time=2013-03-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1802154, encodeId=724018021545c, content=<a href='/topic/show?id=acfae485578' target=_blank style='color:#2F92EE;'>#科学家发现#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74855, encryptionId=acfae485578, topicName=科学家发现)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e572480, createdName=旅苦化文_208, createdTime=Fri Jan 18 00:10:00 CST 2013, time=2013-01-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1714692, encodeId=e5441e1469251, content=<a href='/topic/show?id=021230e312' target=_blank style='color:#2F92EE;'>#AZ#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3073, encryptionId=021230e312, topicName=AZ)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9e5031899089, createdName=12498e5fm22(暂无昵称), createdTime=Fri Oct 26 05:10:00 CST 2012, time=2012-10-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1251856, encodeId=f3a61251856ae, 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=29, 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=Wed Apr 04 11:10:00 CST 2012, time=2012-04-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1480392, encodeId=c04d1480392f5, content=<a href='/topic/show?id=647d2615939' target=_blank style='color:#2F92EE;'>#低剂量#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=26159, encryptionId=647d2615939, topicName=低剂量)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=97b17641126, createdName=ms1292405679162969, createdTime=Wed Apr 04 11:10:00 CST 2012, time=2012-04-04, status=1, ipAttribution=)]
    2012-10-26 12498e5fm22(暂无昵称)

    #AZ#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1868472, encodeId=1f1718684e2b8, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Sun Apr 22 02:10:00 CST 2012, time=2012-04-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1958686, encodeId=76b6195868670, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Mon Feb 04 20:10:00 CST 2013, time=2013-02-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1780561, encodeId=e0971e8056149, content=<a href='/topic/show?id=517a4016ac' target=_blank style='color:#2F92EE;'>#cancer cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, 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=Fri Mar 15 01:10:00 CST 2013, time=2013-03-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1802154, encodeId=724018021545c, content=<a href='/topic/show?id=acfae485578' target=_blank style='color:#2F92EE;'>#科学家发现#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74855, encryptionId=acfae485578, topicName=科学家发现)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e572480, createdName=旅苦化文_208, createdTime=Fri Jan 18 00:10:00 CST 2013, time=2013-01-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1714692, encodeId=e5441e1469251, content=<a href='/topic/show?id=021230e312' target=_blank style='color:#2F92EE;'>#AZ#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3073, encryptionId=021230e312, topicName=AZ)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9e5031899089, createdName=12498e5fm22(暂无昵称), createdTime=Fri Oct 26 05:10:00 CST 2012, time=2012-10-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1251856, encodeId=f3a61251856ae, 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=29, 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=Wed Apr 04 11:10:00 CST 2012, time=2012-04-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1480392, encodeId=c04d1480392f5, content=<a href='/topic/show?id=647d2615939' target=_blank style='color:#2F92EE;'>#低剂量#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=26159, encryptionId=647d2615939, topicName=低剂量)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=97b17641126, createdName=ms1292405679162969, createdTime=Wed Apr 04 11:10:00 CST 2012, time=2012-04-04, status=1, ipAttribution=)]
    2012-04-04 yxch36

    #癌细胞#

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1868472, encodeId=1f1718684e2b8, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Sun Apr 22 02:10:00 CST 2012, time=2012-04-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1958686, encodeId=76b6195868670, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Mon Feb 04 20:10:00 CST 2013, time=2013-02-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1780561, encodeId=e0971e8056149, content=<a href='/topic/show?id=517a4016ac' target=_blank style='color:#2F92EE;'>#cancer cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, 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=Fri Mar 15 01:10:00 CST 2013, time=2013-03-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1802154, encodeId=724018021545c, content=<a href='/topic/show?id=acfae485578' target=_blank style='color:#2F92EE;'>#科学家发现#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74855, encryptionId=acfae485578, topicName=科学家发现)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e572480, createdName=旅苦化文_208, createdTime=Fri Jan 18 00:10:00 CST 2013, time=2013-01-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1714692, encodeId=e5441e1469251, content=<a href='/topic/show?id=021230e312' target=_blank style='color:#2F92EE;'>#AZ#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3073, encryptionId=021230e312, topicName=AZ)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9e5031899089, createdName=12498e5fm22(暂无昵称), createdTime=Fri Oct 26 05:10:00 CST 2012, time=2012-10-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1251856, encodeId=f3a61251856ae, 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=29, 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=Wed Apr 04 11:10:00 CST 2012, time=2012-04-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1480392, encodeId=c04d1480392f5, content=<a href='/topic/show?id=647d2615939' target=_blank style='color:#2F92EE;'>#低剂量#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=26159, encryptionId=647d2615939, topicName=低剂量)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=97b17641126, createdName=ms1292405679162969, createdTime=Wed Apr 04 11:10:00 CST 2012, time=2012-04-04, status=1, ipAttribution=)]
    2012-04-04 ms1292405679162969

    #低剂量#

    0