Novel dihydropyrazole-chromen: Design and modulates hTERT inhibition proliferation of MGC-803
Novel dihydropyrazole-chromen: Design and modulates hTERT inhibition proliferation of MGC-803
复制标题
新型二氢吡唑色烯：设计和调节 hTERT 抑制 MGC-803 的增殖
DOI：
10.1016/j.ejmech.2016.01.014
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发表时间：
2016-03-03
影响因子：
6.7
通讯作者：
Liu, Xin Hua
中科院分区：
文献类型：
--
作者：
Chen, Yan Yan;Wu, Xiao Qin;Liu, Xin Hua
端粒酶hTERT的显性阴性突变体在肿瘤细胞中表现出选择性抗癌作用。但是，目前还没有开发出一种有效的、高选择性的hTERT抑制剂。针对hTERT，设计了一种新的控制hTERT的二氢吡唑-铬胺（13k）。标题化合物13k对mgm -803细胞具有较高的抗增殖活性，IC50值为1.41 μ M，但对人正常胃粘膜细胞表现出明显的无毒作用，IC50值为2.3 mM。探讨化合物13k通过调节hTERT进一步抑制mgm -803细胞的机制，结果表明，化合物13k明显调节hTERT的表达，从而降低β -catenin的活性。从而调节下游信号分子c-myc和cyclin D1的表达，抑制MGC-803细胞的增殖。(C) 2016 Elsevier Masson SAS。版权所有。
Dominant-negative mutant of telomerase hTERT was demonstrated to show selective anticancer effects in tumor cells. But, an effective hTERT inhibitor with high selectivity has not been developed so far. Focused on hTERT, a novel dihydropyrazole-chromen (13k) controlling hTERT was designed. Title compound 13k occupied high antiproliferative activity against MGC-803 cells with IC50 value 1.41 mu M, but it manifested obvious un-toxic effect on human normal gastric mucosa cells with the IC50 2.3 mM. Treated with compound 13k, the further inhibition mechanisms by modulating hTERT was explored, the results showed that expression of hTERT was clearly modulated, and then beta-catenin activation was decreased, thereby the expression of downstream signaling molecules including c-myc and cyclin D1 was modulated, leading to inhibition MGC-803 cells proliferation. (C) 2016 Elsevier Masson SAS. All rights reserved.