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七氟醚通过上调启动子区域的DNA甲基化状态,减弱舌鳞状细胞癌细胞中缺氧诱导的血管内皮生长因子(VEGF)水平。

Sevoflurane attenuate hypoxia-induced VEGF level in tongue squamous cell carcinoma cell by upregulating the DNA methylation states of the promoter region.

作者信息

Lu Yi, Wang Jing, Yan Jia, Yang Yaqiong, Sun Yu, Huang Yan, Hu Rong, Zhang Ying, Jiang Hong

机构信息

Department of Anaesthesiology, Department of plastic and reconstructive surgery, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.

Department of Anaesthesiology, Department of plastic and reconstructive surgery, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.

出版信息

Biomed Pharmacother. 2015 Apr;71:139-45. doi: 10.1016/j.biopha.2015.02.032. Epub 2015 Mar 3.

Abstract

Anaesthetic agents were confirmed to play a role on the tumor angiogenesis. The effect of sevoflurane on tongue squamous cell carcinoma (TSCC) cell has not been investigated. SCC-4 cells were exposed to sevoflurane after simulating hypoxia. Then, both the mRNA and protein level of hypoxia-inducible factor (HIF)-1α and VEGF were detected. The methylation states of the VEGF promoter region were also assessed to reveal the underlying mechanism. Finally, the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-Aza) was administrated to reveal the relationship of DNA methylation on the regulation of the VEGF level. Results showed that sevoflurane attenuated the hypoxia-induced VEGF level without altering the HIF-1α after exposure for 24 and 72 h. Sevoflurane increased the DNA methylation of the VEGF promoter region. The attenuation effect of sevoflurane on hypoxia-induced VEGF level could be blocked by 5-Aza. We concluded that sevoflurane attenuates hypoxia-induced VEGF level via DNA methylation of the promoter region in TSCC cell.

摘要

麻醉剂被证实对肿瘤血管生成有作用。七氟醚对舌鳞状细胞癌(TSCC)细胞的影响尚未得到研究。在模拟缺氧后,将SCC - 4细胞暴露于七氟醚中。然后,检测缺氧诱导因子(HIF)-1α和血管内皮生长因子(VEGF)的mRNA和蛋白水平。还评估了VEGF启动子区域的甲基化状态以揭示潜在机制。最后,给予DNA甲基转移酶抑制剂5-氮杂-2'-脱氧胞苷(5-Aza)以揭示DNA甲基化与VEGF水平调节之间的关系。结果显示,暴露24小时和72小时后,七氟醚减弱了缺氧诱导的VEGF水平,而未改变HIF-1α。七氟醚增加了VEGF启动子区域的DNA甲基化。5-Aza可阻断七氟醚对缺氧诱导的VEGF水平的减弱作用。我们得出结论,七氟醚通过TSCC细胞中启动子区域的DNA甲基化减弱缺氧诱导的VEGF水平。

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