5-偶氮胞苷和丙戊酸对肝癌WCH-17细胞表观遗传修饰DNMT1基因表达、凋亡诱导和细胞活力的影响

M. Sanaei, F. Kavoosi
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引用次数: 14

摘要

背景:真核细胞的DNA分子以一种名为染色质的核蛋白复合体的形式存在。两种表观遗传修饰对基因的转录控制至关重要,包括乙酰化和DNA甲基化。肿瘤抑制基因的高甲基化是由多种DNA甲基转移酶(dnmtts)催化的,包括DNMT1、DNMT2和DNMT3。最具代表性的DNA去甲基化和组蛋白去乙酰化酶抑制剂药物分别是5-aza-2脱氧胞苷(5-Aza-CdR)和丙戊酸(VPA)。本研究的目的是分析5-Aza-CdR和VPA对WCH-17肝癌细胞系细胞生长、凋亡和DNMT1基因表达的影响。材料和方法:在这项描述性分析研究中,采用MTT法、流式细胞术和定量实时荧光定量pcr来评估细胞的增殖和凋亡作用以及基因表达。结果:两种化合物均能抑制细胞生长,诱导细胞凋亡,且呈剂量依赖性和时间依赖性。此外,5-Aza-CdR下调DNMT1基因的表达。DNMT1在不同时间的相对表达量分别为0.40和0.20 (P < 0.001)。VPA处理后的凋亡细胞百分比分别减少了约28%和34% (P小于0.001),5- aza - cdr处理后的凋亡细胞百分比分别减少了约34%和44% (P小于0.001)。结论:在本研究中,我们观察到5-Aza-CdR和VPA能够显著抑制WCH-17细胞的生长,并在凋亡中发挥重要作用。还发现5-Aza-CdR可以降低DNMT1基因的表达。
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Effects of 5-aza-2ˈ-deoxycytidine and Valproic Acid on Epigenetic-modifying DNMT1 Gene Expression, Apoptosis Induction and Cell Viability in Hepatocellular Carcinoma WCH-17 cell line
Background: DNA molecule of the eukaryotic cells is found in the form of a nucleoprotein complex named chromatin. Two epigenetic modifications are critical for transcriptional control of genes, including acetylation and DNA methylation. Hypermethylation of tumor suppressor genes is catalyzed by various DNA methyltransferase enzymes (DNMTs), including DNMT1, DNMT2, and DNMT3. The most well characterized DNA demetilating and histone deacetylase inhibitor drugs are 5-aza-2ˈ-deoxycytidine (5-Aza-CdR) and valproic acid (VPA), respectively. The purpose of the current study was to analyze the effects of 5-Aza-CdR and VPA on cell growth, apoptosis, and DNMT1 gene expression in the WCH-17 hepatocellular carcinoma (HCC) cell line. Materials and Methods: In this descriptive analytical study, MTT assay, flow cytometry assay, and Quantitative Real-Time RT-PCRwere done to evaluate proliferative and apoptotic effects and also gene expression. Results: Both compounds inhibited the cell growth and induced apoptosis significantly in a dose and time depended fashion. Additionally, 5-Aza-CdR down-regulated DNMT1 gene expression. The relative expression of DNMT1 was 0.40 and 0.20 (P < 0.001) at different times, respectively. The percentage of VPA- treated apoptotic cells were reduced by about 28 and 34 % (P˂0.001) and that of 5-Aza-CdR-treated were reduced by about 34 and 44 % (P˂0.001) after treatment time periods. Conclusion: In the current study, it was observed that 5-Aza-CdR and VPA could significantly inhibit the growth of WCH-17 cell and played a significant role in apoptosis. It was also found that 5-Aza-CdR could decrease DNMT1 gene expression.
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CiteScore
0.80
自引率
33.30%
发文量
33
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