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姜黄素对雌激素受体α基因表达的再激活、细胞生长抑制和诱导肝癌 Hepa 1-6 细胞系凋亡的作用与 Trichostatin A 的比较。

Effect of Curcumin in Comparison with Trichostatin A on the Reactivation of Estrogen Receptor Alpha gene Expression, Cell Growth Inhibition and Apoptosis Induction in Hepatocellular Carcinoma Hepa 1-6 Cell lLine.

机构信息

Research Center for Non-Communicable Diseases, Jahrom University of Medical Sciences, Jahrom, Iran.

Student of Research Committee, Jahrom University of Medical Sciences, Jahrom, Iran.

出版信息

Asian Pac J Cancer Prev. 2020 Apr 1;21(4):1045-1050. doi: 10.31557/APJCP.2020.21.4.1045.

Abstract

BACKGROUND

A multistep process with an accumulation of epigenetic alterations of tumor suppressor genes (TSGs) can induce cancer. Abnormal regional hypermethylation and histone deacetylation of several TSGs has been observed in hepatocellular carcinoma (HCC). Acetylation and deacetylation of histone are carried out by histone acetyltransferase (HAT) and histone deacetylase (HDAC) respectively. Besides, DNA methylation is carried out by DNA methyltransferases (DNMTs). Previously, we evaluated the effect of DNA demethylating agents and histone deacetylase inhibitors on HCC and colon cancer. This study aimed to evaluate the effect of curcumin (CUR) in comparison with trichostatin A (TSA) on estrogen receptor alpha (ERα) reactivation, apoptotic induction, and cell growth inhibition in HCC.

METHODS

the cells were cultured and treated with various concentrations of CUR and TSA and the MTT assay, flow cytometry assay and Real-Time RT-PCR were achieved to determine cell viability, cell apoptosis, and ERα gene expression respectively.

RESULTS

CUR indicated dose and time-dependent antiproliferative effects (P < 0.035). A similar antiproliferative effect was observed by TSA (P < 0.001). Both compounds indicated significant apoptotic effects in all different periods (P < 0.001), CUR indicated a more significant apoptotic effect than TSA (P < 0.001). The ERα gene expression quantity was increased significantly by treatment with CUR and TSA (P <0.012).

CONCLUSION

CUR and TSA play important roles in restoring the ERα resulting in cell growth inhibition and apoptosis induction. Therefore, ERα may be a potential target for therapeutic intervention in the treatment of HCC.

摘要

背景

肿瘤抑制基因 (TSGs) 的表观遗传改变的多步骤过程可诱发癌症。已在肝细胞癌 (HCC) 中观察到几个 TSG 的异常区域性高甲基化和组蛋白去乙酰化。组蛋白的乙酰化和去乙酰化分别由组蛋白乙酰转移酶 (HAT) 和组蛋白去乙酰化酶 (HDAC) 进行。此外,DNA 甲基化由 DNA 甲基转移酶 (DNMTs) 进行。以前,我们评估了 DNA 去甲基化剂和组蛋白去乙酰化酶抑制剂对 HCC 和结肠癌的作用。本研究旨在评估姜黄素 (CUR) 与曲古抑菌素 A (TSA) 相比对 HCC 中雌激素受体 alpha (ERα) 再激活、凋亡诱导和细胞生长抑制的作用。

方法

将细胞培养并用不同浓度的 CUR 和 TSA 处理,通过 MTT 测定法、流式细胞术测定法和实时 RT-PCR 分别测定细胞活力、细胞凋亡和 ERα 基因表达。

结果

CUR 呈剂量和时间依赖性的抗增殖作用 (P < 0.035)。TSA 也表现出类似的抗增殖作用 (P < 0.001)。两种化合物在所有不同时期均表现出显著的凋亡作用 (P < 0.001),CUR 的凋亡作用比 TSA 更显著 (P < 0.001)。CUR 和 TSA 处理后 ERα 基因表达量显著增加 (P < 0.012)。

结论

CUR 和 TSA 在恢复 ERα 方面发挥重要作用,导致细胞生长抑制和凋亡诱导。因此,ERα 可能是治疗 HCC 的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f732/7445996/8805b06678d4/APJCP-21-1045-g001.jpg

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