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基于选择性多巴胺受体D2激动剂和拮抗剂对MCF-7细胞系作用的乳腺癌新视角疗法

New perspective therapy of breast cancer based on selective dopamine receptor D2 agonist and antagonist effects on MCF-7 cell line.

作者信息

Pornour Majid, Ahangari Ghasem, Hejazi Seyed H, Deezagi Abdolkhalegh

机构信息

Neuroimmunopsychooncogenetic Group, Division of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, P.O. Box: 14965/161, Tehran, Iran.

出版信息

Recent Pat Anticancer Drug Discov. 2015;10(2):214-23. doi: 10.2174/1574892810666150416111831.

Abstract

Different studies have shown the role of neurotransmitters (e.g., dopamine) in the progression of cancers via their various types of receptors. The aim of this study was to determine the pattern of dopamine receptors gene expression on MCF-7 cells and to evaluate the selective dopamine receptors agonist and antagonist effects on them. In addition, some other discoveries which are patented for the treatment of breast cancer are reviewed in this article. To determine the pattern of dopamine receptors gene expression in human breast cancer cells (MCF-7), RT-PCR was performed. Then, MCF-7 cells were treated by different doses of bromocriptine and remoxipride for 48 hours. Cell viability was evaluated by MTT assay. Thus, nuclear morphology of cells was analyzed by mixed dye florescent staining. Real time PCR technique was performed to determine the decreasing rate of proliferating cell nuclear antigen (PCNA) gene expression in treated MCF-7 cells. Finally, quantification of apoptosis and its difference with necrosis at the single cell level were assessed by Flowcytometery technique. This study revealed that, unlike remoxipride, bromocriptine suppressed proliferation of the MCF-7 cells (54.3% at 12.5µM bromocriptine concentration), but remoxipride could suppress the effect of bromocriptine. Bromocriptine has inhibitory effects on MCF- 7 cells by induction of apoptosis via D2-like receptors. Therefore, in future studies, bromocriptine can be used as a new choice for the treatment of tumoral breast cancer cells.

摘要

不同的研究表明神经递质(如多巴胺)通过其各种类型的受体在癌症进展中所起的作用。本研究的目的是确定多巴胺受体基因在MCF-7细胞上的表达模式,并评估选择性多巴胺受体激动剂和拮抗剂对它们的作用。此外,本文还综述了一些已获专利的用于治疗乳腺癌的其他发现。为了确定人乳腺癌细胞(MCF-7)中多巴胺受体基因的表达模式,进行了逆转录聚合酶链反应(RT-PCR)。然后,用不同剂量的溴隐亭和瑞莫必利处理MCF-7细胞48小时。通过MTT法评估细胞活力。因此,通过混合染料荧光染色分析细胞的核形态。采用实时PCR技术测定经处理的MCF-7细胞中增殖细胞核抗原(PCNA)基因表达的下降率。最后,通过流式细胞术技术评估单细胞水平上细胞凋亡的定量及其与坏死的差异。本研究表明,与瑞莫必利不同,溴隐亭可抑制MCF-7细胞的增殖(溴隐亭浓度为12.5µM时抑制率为54.3%),但瑞莫必利可抑制溴隐亭的作用。溴隐亭通过D2样受体诱导细胞凋亡,对MCF-7细胞具有抑制作用。因此,在未来的研究中,溴隐亭可作为治疗乳腺肿瘤细胞的新选择。

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