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新型组蛋白去乙酰化酶抑制剂西达本胺诱导人结肠癌细胞凋亡。

A novel histone deacetylase inhibitor Chidamide induces apoptosis of human colon cancer cells.

机构信息

Department of Oncology, Zhong-Da Hospital of Southeast University, Nanjing 210009, Jiangsu, PR China.

出版信息

Biochem Biophys Res Commun. 2010 Feb 5;392(2):190-5. doi: 10.1016/j.bbrc.2010.01.011. Epub 2010 Jan 7.

Abstract

Many studies have demonstrated that histone deacetylase (HDAC) inhibitors induce various tumor cells to undergo apoptosis, and such inhibitors have been used in different clinical trials against different human cancers. In this study, we designed and synthesized a novel HDAC inhibitor, Chidamide. We showed that Chidamide was able to increase the acetylation levels of histone H3 and to inhibit the PI3K/Akt and MAPK/Ras signaling pathways, which resulted in arresting colon cancer cells at the G1 phase of the cell cycle and promoting apoptosis. As a result, the proliferation of colon cancer cells was suppressed in vitro. Our data support the potential application of Chidamide as an anticancer agent in treating colon cancer. Future studies are needed to demonstrate its in vivo efficacy.

摘要

许多研究表明组蛋白去乙酰化酶(HDAC)抑制剂可诱导多种肿瘤细胞发生凋亡,此类抑制剂已在不同的临床试验中用于治疗不同类型的人类癌症。在本研究中,我们设计并合成了一种新型的 HDAC 抑制剂,西达本胺。我们发现西达本胺能够增加组蛋白 H3 的乙酰化水平,并抑制 PI3K/Akt 和 MAPK/Ras 信号通路,导致结肠癌细胞停滞在细胞周期的 G1 期,并促进细胞凋亡。因此,体外结肠癌细胞的增殖受到抑制。我们的数据支持将西达本胺作为治疗结肠癌的抗癌药物的潜在应用。需要进一步的研究来验证其体内疗效。

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