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β-榄香烯对 H22 腹水肝癌细胞系组蛋白 H1 的潜在作用。

Potential role of β-elemene on histone H1 in the H22 ascites hepatoma cell line.

机构信息

Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, PR China.

出版信息

Mol Med Rep. 2012 Jul;6(1):185-90. doi: 10.3892/mmr.2012.891. Epub 2012 Apr 26.

Abstract

β-Elemene is extracted from the Chinese medicinal herb Curcuma Wenyujin. It has a broad-spectrum antitumor effect on many types of cancer. However, the exact mechanism of action of β-elemene in hepatocellular carcinoma (HCC) remains unknown. Histone H1 is thought to act as a repressor of transcription by promoting the compaction of chromatin into higher order structures. We found that histone H1 plays an important role in the antitumor function of β-elemene. In this study, histone H1 expression in the H22 murine hepatocellular carcinoma cell line was confirmed, with P388D1 cells serving as a positive control. Furthermore, H22 cells were cultured with β-elemene for different time-points in vitro and treated with different dose-dependent β-elemene in an experimental H22 HCC xenograft transplantation model to confirm whether β-elemene inhibited the growth of H22 tumor cells. In addition, measurements of histone H1 expression both in vitro and in vivo enabled us to demonstrate that β-elemene affects the expression of histone H1 only at the protein level, but is not involved in regulation at the gene level. Our results clearly show that the effect of β-elemene on inhibiting the growth of H22 tumor cells is time- and dose-dependent. In conclusion, β-elemene inhibits the growth of H22 cells by enhancing the expression of histone H1 only at the protein level. This finding may provide insight into a new mechanism of the antitumor action of β-elemene.

摘要

β-榄香烯从中国草药莪术中提取,对多种癌症具有广谱的抗肿瘤作用。然而,β-榄香烯在肝癌(HCC)中的确切作用机制尚不清楚。组蛋白 H1 被认为通过促进染色质凝聚成更高阶结构来充当转录的抑制剂。我们发现组蛋白 H1 在β-榄香烯的抗肿瘤功能中起重要作用。在这项研究中,确认了 H22 鼠肝癌细胞系中组蛋白 H1 的表达,以 P388D1 细胞作为阳性对照。此外,体外培养 H22 细胞不同时间点,并在实验性 H22 HCC 异种移植移植模型中用不同剂量依赖性β-榄香烯处理,以确认β-榄香烯是否抑制 H22 肿瘤细胞的生长。此外,在体外和体内测量组蛋白 H1 的表达使我们能够证明β-榄香烯仅在蛋白质水平上影响组蛋白 H1 的表达,而不涉及基因水平的调节。我们的结果清楚地表明,β-榄香烯抑制 H22 肿瘤细胞生长的作用呈时间和剂量依赖性。总之,β-榄香烯通过仅在蛋白质水平上增强组蛋白 H1 的表达来抑制 H22 细胞的生长。这一发现可能为β-榄香烯的抗肿瘤作用提供新的机制见解。

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