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组蛋白去乙酰化酶抑制剂辛二酰双羟肟酸抑制乳腺癌细胞增殖并诱导其凋亡。

Histone deacetylase inhibitor suberoyl bis-hydroxamic acid suppresses cell proliferation and induces apoptosis in breast cancer cells.

作者信息

Yang Xinmiao, Zhang Ning, Shi Zeliang, Yang Zhangyu, Hu Xichun

机构信息

Department of Medical Oncology, Minhang Branch of Fudan University Shanghai Cancer Center, Shanghai 200240, P.R. China.

Department of Radiation Oncology, Affiliated Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai 200233, P.R. China.

出版信息

Mol Med Rep. 2015 Apr;11(4):2908-12. doi: 10.3892/mmr.2014.3076. Epub 2014 Dec 11.

Abstract

Suberoyl bis‑hydroxamic acid (SBHA) is a histone deacetylase inhibitor that has shown anticancer activity against numerous types of human cancer. The aim of the current study was to explore the effects of SBHA on the proliferation and apoptosis of breast cancer cells. MCF‑7 breast cancer cells were treated with different concentrations of SBHA and tested for cell viability, apoptosis and gene expression changes. The results showed that SBHA significantly inhibited the proliferation of MCF‑7 cells in a concentration‑dependent manner, as determined using a Cell Counting kit‑8 assay. SBHA‑treated MCF‑7 cells showed G0/G1 cell‑cycle arrest, coupled with elevated expression levels of p21 and p27 proteins. Hoechst 33258 staining revealed cell shrinkage, chromosomal condensation and nuclear fragmentation in MCF‑7 cells treated with SBHA. Flow cytometric analysis of Annexin V‑stained cells showed that SBHA treatment induced apoptotic cell death in a concentration‑dependent manner. Western blot analysis confirmed the upregulation of Bax and the downregulation of Bcl‑2 by SBHA. In conclusion, these results indicate that SBHA exerts cytotoxic effects against human breast cancer cells, which involves the modulation of p21, p27 and Bcl‑2 family proteins, consequently leading to cell‑cycle arrest and apoptosis.

摘要

辛二酰双羟肟酸(SBHA)是一种组蛋白脱乙酰酶抑制剂,已显示出对多种人类癌症的抗癌活性。本研究的目的是探讨SBHA对乳腺癌细胞增殖和凋亡的影响。用不同浓度的SBHA处理MCF-7乳腺癌细胞,并检测细胞活力、凋亡和基因表达变化。结果表明,使用细胞计数试剂盒-8检测法确定,SBHA以浓度依赖性方式显著抑制MCF-7细胞的增殖。经SBHA处理的MCF-7细胞出现G0/G1期细胞周期阻滞,同时p21和p27蛋白表达水平升高。Hoechst 33258染色显示,经SBHA处理的MCF-7细胞出现细胞皱缩、染色体浓缩和核碎裂。对Annexin V染色细胞进行流式细胞术分析表明,SBHA处理以浓度依赖性方式诱导凋亡细胞死亡。蛋白质印迹分析证实,SBHA使Bax上调,Bcl-2下调。总之,这些结果表明,SBHA对人乳腺癌细胞具有细胞毒性作用,这涉及对p21、p27和Bcl-2家族蛋白的调节,从而导致细胞周期阻滞和凋亡。

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