Cancer Prev Res：新药物或可阻断肥胖相关癌基因！

2018-04-01 Ruthy，Yui 转化医学网

有证据表明，近50万新发癌症病例与肥胖有关。我们知道c-Myc基因由内脏脂肪诱导，而高脂肪饮食可造成内脏脂肪的大量累积，诱导c-Myc基因的表达，因此肥胖可增加癌症风险。c-myc基因是myc基因家族的重要成员之一，是一种可使细胞无限增殖，获永生化功能，促进细胞分裂的基因，c-myc基因与多种肿瘤发生发展有关。对于这些肥胖相关癌症，能否从基因这个根源上彻底阻断呢？

有证据表明，近50万新发癌症病例与肥胖有关。我们知道c-Myc基因由内脏脂肪诱导，而高脂肪饮食可造成内脏脂肪的大量累积，诱导c-Myc基因的表达，因此肥胖可增加癌症风险。c-myc基因是myc基因家族的重要成员之一，是一种可使细胞无限增殖，获永生化功能，促进细胞分裂的基因，c-myc基因与多种肿瘤发生发展有关。对于这些肥胖相关癌症，能否从基因这个根源上彻底阻断呢？

最新消息称，目前密歇根州立大学的科学家们正在测试一种极具发展前景的新药，或可阻断c-myc基因，同时阻止相关癌症的发展。这些进展均基于最新一期《Cancer Prevention Research 》中的两项相关研究。

首先是该校药理学和毒理学系副教授Karen Liby领导的临床前研究，研究结果显示药物I-BET-762-762可阻断癌基因c-Myc的表达，从而显著延缓了乳腺癌和肺癌的发展。I-BET-762 762是新的溴结构域抑制剂，其可逆地靶向BET（溴结构域和外部末端）蛋白质并且阻止它们与组蛋白上的乙酰化赖氨酸结合，从而中下游转录。这种抑制剂具有抗炎作用并在许多癌症中诱导生长，目前正在进行用于治疗癌症的临床试验。

I-BET-762-762延缓肿瘤发展

I-BET-762-762抑制pSTAT3表达

研究人员发现I-BET-762-762可靶向目标DNA，导致基因c-Myc无法表达，从而有效抑制癌细胞和免疫细胞中许多重要蛋白质的功能，进而抑制癌细胞的生长扩散，最终实验小鼠的癌细胞的数量减少了80％。在癌细胞的发生发展中，c-Myc表达的蛋白至关重要。其中，一旦pSTAT3在免疫细胞中被激活，就会阻断免疫作用，破坏机体免疫功能，导致癌症进一步发展。同时pSTAT3还可在癌细胞中过量表达，将肿瘤细胞隔绝于免疫系统之外，导致肿瘤细胞肆意生长，不受控制。在这项研究中，I-BET-762-762成功使pSTAT3水平降低了50％。

紧接着，药理学和毒理学助理教授Jamie Bernard领导的研究小组将Liby的发现成功地应用于癌前细胞。他们使用软琼脂测定法测量细胞转化，直接观察I-BET-762-762对尚未癌变但具有癌变可能的人体细胞的影响，他们发现，新药物阻止了一半以上的这些细胞发生癌变。

I-BET-762-762显著抑制癌前细胞的生长

同时，研究人员还发现I-BET-762使c-Myc过表达细胞中的软琼脂减少了20％，而单独c-Myc的过表达可刺激软琼脂中的生长，软琼脂的减少与c-Myc蛋白质表达的下调相关，这表明I-BET-762具有c-Myc依赖性和非依赖性活性。他们还证明I-BET-762对细胞转化的作用可能不局限于表皮，在其他组织中可能也会发挥作用，实验中I-BET-762减弱了两种人乳腺上皮细胞NMuMG和MCF-10A中HuFTF的转化活性。

I-BET-762-762减弱了两种人乳腺上皮细胞NMuMG和MCF-10A中HuFTF的转化活性

尽管目前的癌症治疗使癌症死亡率有一定程度的降低，但与肥胖相关的癌症数量仍在不断攀升。另一方面，目前研究人员在降低乳腺癌和肺癌的高死亡率方面的成效有限，因此迫切需要对这些疾病采取新的预防方法。目前I-BET-762-762的类似药物在各种其他癌症中的应用正处于临床试验中，包括白血病，淋巴瘤，脑肿瘤和骨髓瘤，希望I-BET-762-762能够提高乳腺癌和肺癌患者的生存率。

原始出处：

Debrup Chakraborty, et al.A BET Bromodomain Inhibitor Suppresses Adiposity-Associated Malignant Transformation.Cancer Prev Res March 1 2018 11 (3) 129-142; DOI:10.1158/1940-6207.CAPR-17-0262

Di Zhang, et al.Chemoprevention of Preclinical Breast and Lung Cancer with the Bromodomain Inhibitor I-BET 762.Cancer Prev Res March 1 2018 11 (3) 143-156; DOI:10.1158/1940-6207.CAPR-17-0264

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2018-06-29 ms1065684921169360

#新药物#

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2018-04-08 jihuaijun1112

学习学习学习.

89 0
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2018-04-08 wzb521zf

一起学习学习

124 0
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2018-08-29 41514497@qq.com

#阻断#

65 0
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2018-04-07 jihuaijun1112

学习学习学习

96 0
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2018-04-07 wzb521zf

一起学习学习

83 0
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2018-04-06 wzb521zf

一起学习学习学习

82 0
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2018-04-06 jihuaijun1112

学习学习学习学习

63 0
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createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzR8ylhYfiaoAUx2BsaYHVia1IKhG3Cg8CT84rBrn6iaVRkyAibJxBcLEXabOQ5p19vWgDe34ib5ErxNgx/0, createdBy=8a701629084, createdName=jihuaijun1112, createdTime=Sun Apr 08 00:56:51 CST 2018, time=2018-04-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=303700, encodeId=9fca303e008a, content=一起学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=124, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/TDiaAWyicHgedzX3wKo3qcxudVJib7AfibfvNeufHRF2jG3Bw8MmZyWjIhtBV1mpJI7Sy9n7RcBKK5t3CuOKuOFxkg/0, createdBy=dd702206933, createdName=wzb521zf, createdTime=Sun Apr 08 00:16:45 CST 2018, time=2018-04-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1710128, encodeId=08151e10128f5, content=<a href='/topic/show?id=7ac59e67604' target=_blank style='color:#2F92EE;'>#阻断#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97676, encryptionId=7ac59e67604, topicName=阻断)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b5ca31824852, createdName=41514497@qq.com, createdTime=Wed Aug 29 19:00:00 CST 2018, time=2018-08-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=303416, encodeId=5aab30341628, content=学习学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=96, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzR8ylhYfiaoAUx2BsaYHVia1IKhG3Cg8CT84rBrn6iaVRkyAibJxBcLEXabOQ5p19vWgDe34ib5ErxNgx/0, createdBy=8a701629084, createdName=jihuaijun1112, createdTime=Sat Apr 07 01:22:10 CST 2018, time=2018-04-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=303404, encodeId=a5b1303404e5, content=一起学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/TDiaAWyicHgedzX3wKo3qcxudVJib7AfibfvNeufHRF2jG3Bw8MmZyWjIhtBV1mpJI7Sy9n7RcBKK5t3CuOKuOFxkg/0, createdBy=dd702206933, createdName=wzb521zf, createdTime=Sat Apr 07 00:20:44 CST 2018, time=2018-04-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=303285, encodeId=b58a3032858d, content=一起学习学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/TDiaAWyicHgedzX3wKo3qcxudVJib7AfibfvNeufHRF2jG3Bw8MmZyWjIhtBV1mpJI7Sy9n7RcBKK5t3CuOKuOFxkg/0, createdBy=dd702206933, createdName=wzb521zf, createdTime=Fri Apr 06 12:16:13 CST 2018, time=2018-04-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=303130, encodeId=e04c3031306e, content=学习学习学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzR8ylhYfiaoAUx2BsaYHVia1IKhG3Cg8CT84rBrn6iaVRkyAibJxBcLEXabOQ5p19vWgDe34ib5ErxNgx/0, createdBy=8a701629084, createdName=jihuaijun1112, createdTime=Fri Apr 06 00:58:58 CST 2018, time=2018-04-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=302896, encodeId=56f4302896d5, content=一起学习学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/TDiaAWyicHgedzX3wKo3qcxudVJib7AfibfvNeufHRF2jG3Bw8MmZyWjIhtBV1mpJI7Sy9n7RcBKK5t3CuOKuOFxkg/0, createdBy=dd702206933, createdName=wzb521zf, createdTime=Thu Apr 05 07:32:56 CST 2018, time=2018-04-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=302621, encodeId=24eb30262167, content=一起学习学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/TDiaAWyicHgedzX3wKo3qcxudVJib7AfibfvNeufHRF2jG3Bw8MmZyWjIhtBV1mpJI7Sy9n7RcBKK5t3CuOKuOFxkg/0, createdBy=dd702206933, createdName=wzb521zf, createdTime=Wed Apr 04 08:18:26 CST 2018, time=2018-04-04, status=1, ipAttribution=)]
2018-04-05 wzb521zf

一起学习学习学习

67 0
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createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzR8ylhYfiaoAUx2BsaYHVia1IKhG3Cg8CT84rBrn6iaVRkyAibJxBcLEXabOQ5p19vWgDe34ib5ErxNgx/0, createdBy=8a701629084, createdName=jihuaijun1112, createdTime=Sun Apr 08 00:56:51 CST 2018, time=2018-04-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=303700, encodeId=9fca303e008a, content=一起学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=124, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/TDiaAWyicHgedzX3wKo3qcxudVJib7AfibfvNeufHRF2jG3Bw8MmZyWjIhtBV1mpJI7Sy9n7RcBKK5t3CuOKuOFxkg/0, createdBy=dd702206933, createdName=wzb521zf, createdTime=Sun Apr 08 00:16:45 CST 2018, time=2018-04-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1710128, encodeId=08151e10128f5, content=<a href='/topic/show?id=7ac59e67604' target=_blank style='color:#2F92EE;'>#阻断#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97676, encryptionId=7ac59e67604, topicName=阻断)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b5ca31824852, createdName=41514497@qq.com, createdTime=Wed Aug 29 19:00:00 CST 2018, time=2018-08-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=303416, encodeId=5aab30341628, content=学习学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=96, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzR8ylhYfiaoAUx2BsaYHVia1IKhG3Cg8CT84rBrn6iaVRkyAibJxBcLEXabOQ5p19vWgDe34ib5ErxNgx/0, createdBy=8a701629084, createdName=jihuaijun1112, createdTime=Sat Apr 07 01:22:10 CST 2018, time=2018-04-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=303404, encodeId=a5b1303404e5, content=一起学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/TDiaAWyicHgedzX3wKo3qcxudVJib7AfibfvNeufHRF2jG3Bw8MmZyWjIhtBV1mpJI7Sy9n7RcBKK5t3CuOKuOFxkg/0, createdBy=dd702206933, createdName=wzb521zf, createdTime=Sat Apr 07 00:20:44 CST 2018, time=2018-04-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=303285, encodeId=b58a3032858d, content=一起学习学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/TDiaAWyicHgedzX3wKo3qcxudVJib7AfibfvNeufHRF2jG3Bw8MmZyWjIhtBV1mpJI7Sy9n7RcBKK5t3CuOKuOFxkg/0, createdBy=dd702206933, createdName=wzb521zf, createdTime=Fri Apr 06 12:16:13 CST 2018, time=2018-04-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=303130, encodeId=e04c3031306e, content=学习学习学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzR8ylhYfiaoAUx2BsaYHVia1IKhG3Cg8CT84rBrn6iaVRkyAibJxBcLEXabOQ5p19vWgDe34ib5ErxNgx/0, createdBy=8a701629084, createdName=jihuaijun1112, createdTime=Fri Apr 06 00:58:58 CST 2018, time=2018-04-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=302896, encodeId=56f4302896d5, content=一起学习学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/TDiaAWyicHgedzX3wKo3qcxudVJib7AfibfvNeufHRF2jG3Bw8MmZyWjIhtBV1mpJI7Sy9n7RcBKK5t3CuOKuOFxkg/0, createdBy=dd702206933, createdName=wzb521zf, createdTime=Thu Apr 05 07:32:56 CST 2018, time=2018-04-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=302621, encodeId=24eb30262167, content=一起学习学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/TDiaAWyicHgedzX3wKo3qcxudVJib7AfibfvNeufHRF2jG3Bw8MmZyWjIhtBV1mpJI7Sy9n7RcBKK5t3CuOKuOFxkg/0, createdBy=dd702206933, createdName=wzb521zf, createdTime=Wed Apr 04 08:18:26 CST 2018, time=2018-04-04, status=1, ipAttribution=)]
2018-04-04 wzb521zf

一起学习学习学习

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