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灯盏花素通过调节p53信号通路抑制人结肠癌细胞生长并诱导其凋亡。

Scutellarin suppresses growth and causes apoptosis of human colorectal cancer cells by regulating the p53 pathway.

作者信息

Yang Ning, Zhao Yuying, Wang Zhipeng, Liu Yu, Zhang Yanqiao

机构信息

Department of Oncology, The Affiliated Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.

Department of Clinical and Laboratory Medicine, The Affiliated Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.

出版信息

Mol Med Rep. 2017 Feb;15(2):929-935. doi: 10.3892/mmr.2016.6081. Epub 2016 Dec 28.

Abstract

Scutellarin is a flavonoid isolated from a medicinal herb Scutellaria barbata D. Don and exerts therapeutic effects on cardiovascular diseases. However, it remains unclear whether Scutellarin exhibits anti‑tumor actions on human colon cancer. The current study aimed to investigate whether Scutellarin produces antiproliferative and pro‑apoptotic effects on HCT‑116 human colon cancer cells and to elucidate the mechanisms involved. Human colon cancer cells were exposed to different concentrations of Scutellarin, and cellular growth and apoptosis were evaluated by MTT assay, terminal deoxynucleotidyl transferase‑mediated dUTP nick end labeling (TUNEL) staining, western blot analysis and other assays. A cell viability assay demonstrated that Scutellarin treatment reduced the viability of HCT‑116 cells in a dose‑ and time‑dependent manner. TUNEL staining demonstrated that Scutellarin also induced apoptotic changes in HCT‑116 cells. The expression level of the anti‑apoptotic protein, Bcl‑2 apoptosis regulator (Bcl‑2), was reduced by Scutellarin in HCT‑116 cells, whereas the expression Bcl‑2 associated X apoptosis regulator (Bax) and the activation of caspase‑3 protein were increased by Scutellarin treatment. Further investigation revealed that Scutellarin significantly increased the phosphorylation of p53 protein in HCT‑116 cells. Additionally, suppression of p53 using a specific inhibitor, pifithrin‑α, abrogated the pro‑apoptotic effects of Scutellarin in HCT‑116 cells. Collectively, Scutellarin reduced the viability and induced apoptosis of human colon carcinoma cells, potentially by regulating p53 and Bcl‑2/Bax expression. These data suggested that Scutellarin may be useful as a promising anti‑tumor drug for treating colon cancer.

摘要

灯盏花素是从药用植物半枝莲中分离出的一种黄酮类化合物,对心血管疾病具有治疗作用。然而,灯盏花素对人类结肠癌是否具有抗肿瘤作用仍不清楚。当前研究旨在探究灯盏花素是否对HCT-116人结肠癌细胞产生抗增殖和促凋亡作用,并阐明其中涉及的机制。将人结肠癌细胞暴露于不同浓度的灯盏花素中,通过MTT法、末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(TUNEL)染色、蛋白质印迹分析及其他检测方法评估细胞生长和凋亡情况。细胞活力检测表明,灯盏花素处理以剂量和时间依赖性方式降低了HCT-116细胞的活力。TUNEL染色表明,灯盏花素还诱导了HCT-116细胞的凋亡变化。灯盏花素降低了HCT-116细胞中抗凋亡蛋白Bcl-2凋亡调节因子(Bcl-2)的表达水平,而灯盏花素处理增加了Bcl-2相关X凋亡调节因子(Bax)的表达及半胱天冬酶-3蛋白的激活。进一步研究表明,灯盏花素显著增加了HCT-116细胞中p53蛋白的磷酸化。此外,使用特异性抑制剂pifithrin-α抑制p53可消除灯盏花素对HCT-116细胞的促凋亡作用。总体而言,灯盏花素可能通过调节p53和Bcl-2/Bax表达降低人结肠癌细胞的活力并诱导其凋亡。这些数据表明,灯盏花素可能作为一种有前景的抗肿瘤药物用于治疗结肠癌。

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