Chidamide, a novel histone deacetylase inhibitor, synergistically enhances gemcitabine cytotoxicity in pancreatic cancer cells
Chidamide, a novel histone deacetylase inhibitor, synergistically enhances gemcitabine cytotoxicity in pancreatic cancer cells
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Chidamide 是一种新型组蛋白脱乙酰酶抑制剂，可协同增强吉西他滨对胰腺癌细胞的细胞毒性。
DOI：
10.1016/j.bbrc.2013.03.059
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发表时间：
2013-04-26
影响因子：
3.1
通讯作者：
Yu, Qun
中科院分区：
文献类型：
--
作者：
Qiao, Zhixin;Ren, Suping;Yu, Qun
胰腺癌是一种致命的人类恶性肿瘤，预后极差，迫切需要新的治疗方法。组蛋白去乙酰酶抑制剂(HDACIs)是一类新型抗癌药物，在胰腺癌的临床前模型中显示出良好的抗肿瘤活性。在这项研究中，我们试图确定一种新的HDACi，Chidamide(CS055)，单独或与吉西他滨联合使用对胰腺癌细胞的抗肿瘤作用。胆碱胺处理BxPC-3或PANC-1胰腺癌细胞后，细胞生长停滞，并伴有p21表达的诱导，呈剂量和时间依赖性。当按顺序组合时，奇达胺协同增强吉西他滨诱导的细胞生长停滞和凋亡，伴随着Mcl-1的协同下调和线粒体膜电位的丧失(Delta Psi(M))。Chidamine增强吉西他滨诱导的DNA双链断裂和S期阻滞，并取消G2/M细胞周期检查点，可能是通过抑制CHK1的表达。我们的结果表明，奇达胺有治疗胰腺癌的潜力，特别是与吉西他滨联合使用。(C)2013 Elsevier Inc.保留所有权利。
Pancreatic cancer is a lethal human malignancy with an extremely poor prognosis and urgently requires new therapies. Histone deacetylase inhibitors (HDACIs) represent a new class of anticancer agents and have shown promising antitumor activities in preclinical models of pancreatic cancer. In this study, we sought to determine the antitumor effects of a novel HDACI, chidamide (CS055), in pancreatic cancer cells alone or in combination with gemcitabine. Treatments of BxPC-3 or PANC-1 pancreatic cancer cell lines with chidamide resulted in dose- and time-dependent growth arrest, accompanied by induction of p21 expression. When combined in a sequential schedule, chidamide synergistically enhanced gemcitabine-induced cell growth arrest and apoptosis, accompanied by cooperative downregulation of Mcl-1 and loss of mitochondrial membrane potential (Delta Psi(m)). Chidamide enhanced gemcitabine-induced DNA double-strand breaks and S phase arrest, and abrogated the G2/M cell cycle checkpoint, potentially through suppression of CHK1 expression. Our results suggest that chidamide has a therapeutic potential for treating pancreatic cancer, especially in combination with gemcitabine. (C) 2013 Elsevier Inc. All rights reserved.