Ginsenoside Rh2 inhibits breast cancer cell growth via ERβ-TNFα pathway.

Ginsenoside Rh2 inhibits breast cancer cell growth via ERβ-TNFα pathway.
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人参皂苷 Rh2 通过 ERβ-TNFα 途径抑制乳腺癌细胞生长

DOI:
10.3724/abbs.2022039
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发表时间:
2022-05-25
影响因子:
3.7
通讯作者:
Luo ZY
Luo ZY
中科院分区:
生物学3区
文献类型:
--
作者:
Peng K;Luo T;Li J;Huang J;Dong Z;Liu J;Pi C;Zou Z;Gu Q;Liu O;Zhang JT;Luo ZY

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人参皂苷Rh 2是从人参中提取的一种稀有的人参二醇类化合物,是一种潜在的雌激素受体配体,具有一定的雌激素活性。然而,Rh 2对人乳腺细胞生长抑制的作用及其潜在的分子机制尚未完全了解。在这项研究中,我们通过MTT和集落形成试验检测细胞活力。采用流式细胞仪检测细胞生长和细胞周期,观察Rh 2对细胞增殖的影响。采用qPCR和western blot方法检测雌激素受体(ER)、肿瘤坏死因子α(TNFα)及凋亡相关蛋白的表达。通过转染和抑制剂研究ERα和ERβ的作用机制。在异种移植小鼠中研究了抗肿瘤Rh 2对MCF-7细胞的抗肿瘤作用。结果表明,Rh 2可诱导MCF-7细胞发生凋亡,并使细胞周期阻滞于G1/S期。用rh-Rh 2处理细胞后,ERα蛋白水平下调,ERβ和TNFα的mRNA和蛋白水平上调。我们还发现,TNFα的过度表达是通过上调ERβ启动的TNF Rh 2。此外,在体内,rhBRh 2通过雌激素受体β-TNFα途径诱导MCF-7细胞凋亡。这些结果表明,TNF-α诱导的细胞凋亡和G1/S期阻滞是通过调节ERβ而实现的。
Ginsenoside Rh2 is one of rare panaxidiols extracted from Panax ginseng and a potential estrogen receptor ligand that exhibits moderate estrogenic activity. However, the effect of Rh2 on growth inhibition and its underlying molecular mechanism in human breast cells are not fully understood. In this study, we tested cell viability by MTT and colony formation assays. Cell growth and cell cycle were determined to investigate the effect of ginsenoside Rh2 by flow cytometry. The expressions of estrogen receptors (ERs), TNFα, and apoptosis-related proteins were detected by qPCR and western blot analysis. The mechanisms of ERα and ERβ action were determined using transfection and inhibitors. Antitumor effect of ginsenoside Rh2 against MCF-7 cells was investigated in xenograft mice. Our results showed that ginsenoside Rh2 induced apoptosis and G1/S phase arrest in MCF-7 cells. Treatment of cells with ginsenoside Rh2 down-regulated protein levels of ERα, and up-regulated mRNA and protein levels of ERβ and TNFα. We also found that ginsenoside Rh2-induced TNFα over-expression is through up-regulation of ERβ initiated by ginsenoside Rh2. Furthermore, ginsenoside Rh2 induced MCF-7 cell apoptosis via estrogen receptor β-TNFα pathway in vivo. These results demonstrate that ginsenoside Rh2 promotes TNFα-induced apoptosis and G1/S phase arrest via regulation of ERβ.
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