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丙泊酚促进黑色素瘤细胞凋亡并抑制HOTAIR介导的mTOR/p70S6K信号通路。

Propofol promotes apoptosis and suppresses the HOTAIR-mediated mTOR/p70S6K signaling pathway in melanoma cells.

作者信息

Shang Zhiwei, Feng Haixia, Cui Lisha, Wang Weiping, Fu Hongwei

机构信息

Department of Dermatology, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China.

出版信息

Oncol Lett. 2018 Jan;15(1):630-634. doi: 10.3892/ol.2017.7297. Epub 2017 Oct 31.

DOI:10.3892/ol.2017.7297
PMID:29375720
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5766068/
Abstract

Propofol is an intravenous anesthetic, which is widely used in clinical anesthesia induction and maintenance and is critical in the sedation of patients. However, the functions and mechanisms of propofol on apoptosis of melanoma cells remain unclear. The present study investigated whether propofol promotes cell apoptosis and suppresses the HOX transcript antisense RNA (HOTAIR)-mediated mechanistic target of rapamycin (mTOR) pathway in melanoma cells. B16F10 cells were cultured with different concentrations (0-10 µM) of propofol for 24 or 48 h. Proliferation and apoptosis of B16F10 cells were detected using MTT assay and flow cytometry. The pcDNA 3.1(-)-HOTAIR and pcDNA 3.1(-)-control plasmids were transfected into B16F10 cells using Lipofectamine 2000. In the present study, treatment with propofol significantly reduced viability, and induced apoptosis and caspase-3 activity in melanoma cells. Propofol treatment significantly inhibited HOTAIR expression and the expression of phosphorylated (p)-mTOR and p- p70S6K protein in melanoma cells. Overexpression of HOTAIR significantly increased viability of melanoma cells, and increased HOTAIR, p-mTOR and p-p70S6K protein expression in melanoma cells. These results indicated that propofol promotes apoptosis and suppresses the HOTAIR-mediated mTOR signaling pathway in melanoma cells.

摘要

丙泊酚是一种静脉麻醉剂,广泛应用于临床麻醉诱导和维持,对患者镇静至关重要。然而,丙泊酚对黑色素瘤细胞凋亡的作用及其机制仍不清楚。本研究探讨丙泊酚是否能促进黑色素瘤细胞凋亡并抑制HOX转录反义RNA(HOTAIR)介导的雷帕霉素机制性靶标(mTOR)信号通路。将B16F10细胞用不同浓度(0 - 10 μM)的丙泊酚培养24或48小时。采用MTT法和流式细胞术检测B16F10细胞的增殖和凋亡情况。使用Lipofectamine 2000将pcDNA 3.1(-)-HOTAIR和pcDNA 3.1(-)-对照质粒转染到B16F10细胞中。在本研究中,丙泊酚处理显著降低了黑色素瘤细胞的活力,诱导了细胞凋亡和半胱天冬酶-3活性。丙泊酚处理显著抑制了黑色素瘤细胞中HOTAIR的表达以及磷酸化(p)-mTOR和p-p70S6K蛋白的表达。HOTAIR的过表达显著增加了黑色素瘤细胞的活力,并增加了黑色素瘤细胞中HOTAIR、p-mTOR和p-p70S6K蛋白的表达。这些结果表明,丙泊酚可促进黑色素瘤细胞凋亡并抑制HOTAIR介导的mTOR信号通路。

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本文引用的文献

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A Prospective Clinical Trial Combining Radiation Therapy With Systemic Immunotherapy in Metastatic Melanoma.一项转移性黑色素瘤放疗联合全身免疫治疗的前瞻性临床试验。
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Propofol promotes cell apoptosis via inhibiting HOTAIR mediated mTOR pathway in cervical cancer.丙泊酚通过抑制宫颈癌中HOTAIR介导的mTOR通路促进细胞凋亡。
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Propofol-enhanced autophagy increases motility and angiogenic capacity of cultured human umbilical vascular endothelial cells.丙泊酚增强的自噬增加了培养的人脐静脉血管内皮细胞的运动性和血管生成能力。
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