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首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >The novel quinolone CHM-1 induces DNA damage and inhibits DNA repair gene expressions in a human osterogenic sarcoma cell line.
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The novel quinolone CHM-1 induces DNA damage and inhibits DNA repair gene expressions in a human osterogenic sarcoma cell line.

机译:新型喹诺酮CHM-1可以诱导人甾体肉瘤细胞系中的DNA损伤并抑制DNA修复基因的表达。

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摘要

20-Fluoro-6,7-methylenedioxy-2-phenyl-4-quino-lone (CHM-1) has been reported to induce cell cycle arrest and apoptosis in many types of cancer cells. However, there is no available information to show CHM-1 affecting DNA damage and expression of associated repair genes. Herein, we investigated whether or not CHM-1 induced DNA damage and affected DNA repair gene expression in U-2 OS human osterogenic sarcoma cells. The comet assay showed that incubation of U-2 OS cells with 0, 0.75, 1.5, 3 and 6 muM of CHM-1 led to a longer DNA migration smear (comet tail). DNA gel electrophoresis showed that 3 muM of CHM-1 for 24 and 48 h treatment induced DNA fragmentation in U-2 OS cells. Real-time PCR analysis showed that treatment with 3 muM of CHM-1 for 24 h reduced the mRNA expression levels of ataxia telangiectasia mutated (ATM), ataxia-telangiectasia and Rad3-related (ATR), breast cancer 1, early onset (BRCA1), 14-3-3sigma (14-3-3sigma), DNA-dependent serine/threonine protein kinase (DNA-PK) and O(6)-methylguanine-DNA methyltransferase (MGMT) genes in a time-dependent manner. Taken together, the results indicate that CHM-1 caused DNA damage and reduced DNA repair genes in U-2 OS cells, which may be the mechanism for CHM-1-inhibited cell growth and induction of apoptosis.
机译:据报道20-氟-6,7-亚甲基二氧基-2-苯基-4-喹啉酮(CHM-1)在许多类型的癌细胞中诱导细胞周期停滞和凋亡。但是,没有可用的信息显示CHM-1影响DNA损伤和相关修复基因的表达。在本文中,我们调查了CHM-1是否在U-2 OS人成因肉瘤细胞中诱导DNA损伤并影响DNA修复基因表达。彗星试验表明,将U-2 OS细胞与0、0.75、1.5、3和6μMCHM-1一起孵育会导致更长的DNA迁移涂片(彗尾)。 DNA凝胶电泳显示3μMCHM-1分别在24 h和48 h诱导U-2 OS细胞DNA断裂。实时PCR分析显示,用3μMCHM-1处理24小时可降低共济失调毛细血管扩张突变(ATM),共济失调毛细血管扩张和Rad3相关(ATR),乳腺癌1,早发(BRCA1)的mRNA表达水平。 ),14-3-3sigma(14-3-3sigma),DNA依赖的丝氨酸/苏氨酸蛋白激酶(DNA-PK)和O(6)-甲基鸟嘌呤-DNA甲基转移酶(MGMT)基因以时间依赖的方式。两者合计,结果表明CHM-1导致U-2 OS细胞中的DNA损伤和减少的DNA修复基因,这可能是CHM-1抑制细胞生长和诱导凋亡的机制。

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