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阿法替尼联合Mithramycin A对人肝癌HepG2细胞增殖、凋亡及基因表达的影响 被引量:1
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作者 黄子凌 黄兰姗 +1 位作者 沈思乔 冯振博 《南京医科大学学报(自然科学版)》 CAS CSCD 北大核心 2015年第5期638-643,共6页
目的 :观察阿法替尼(afatinib)联合Mithramycin A(MIT)对人肝癌Hep G2细胞增殖、凋亡的作用以及相关因子表达的影响。方法:将afatinib与MIT单独或联合作用于肝癌Hep G2细胞,采用MTT法测定药物对细胞生长的抑制率,并运用倒置显微镜观察... 目的 :观察阿法替尼(afatinib)联合Mithramycin A(MIT)对人肝癌Hep G2细胞增殖、凋亡的作用以及相关因子表达的影响。方法:将afatinib与MIT单独或联合作用于肝癌Hep G2细胞,采用MTT法测定药物对细胞生长的抑制率,并运用倒置显微镜观察药物作用后细胞形态学变化;以流式细胞技术测定药物对细胞周期和凋亡的影响;以实时荧光定量聚合酶链反应(q RT-PCR)定量测定细胞内表皮生长因子受体(EGFR)、Sp1、Sp3以及增殖、凋亡相关因子Cyclin-D1、Cyclin-E2、Bcl-2、Caspase3、Caspase9和p53的表达变化。结果 :afatinib与MIT均能有效抑制肝癌Hep G2细胞的生长,并且呈现时间依赖性,两药联合作用能明显增加抑制率(P均<0.05);联合用药48 h后,可诱导Hep G2细胞产生G0/G1期阻滞并诱发凋亡,抑制作用及凋亡率均较单药组增高(P均<0.05);另外,给药72 h后,单药组均出现不同程度的Cyclin-D1、Cyclin-E2、Bcl-2 m RNA表达量下降,并伴有Caspase3基因上调。单用afatinib组同时出现Caspase9和p53的表达上调,MIT组检测到EGFR、Sp1和Sp3的同步减少,联合用药组以上改变较单药组明显(P均<0.05)。结论:afatinib联合MIT能有效抑制肝癌Hep G2细胞增殖、促进凋亡,这可能与药物作用后Cyclin-D1、Cyclin-E2、Bcl-2下调以及Caspase3、Caspase9和p53的表达上调相关。此项研究可能为以EGFR为中心的肝癌联合治疗提供新方向。 展开更多
关键词 肝细胞癌 HEPG2细胞 阿法替尼 mithramycin a 表皮生长因子受体 SP1
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Gene environment interaction in periphery and brain converge to modulate behavioral outcomes:Insights from the SP1 transient early in life interference rat model 被引量:1
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作者 Eyal Asor Dorit Ben-Shachar 《World Journal of Psychiatry》 SCIE 2016年第3期294-302,共9页
It is generally assumed that behavior results from an interaction between susceptible genes and environmental stimuli during critical life stages.The present article reviews the main theoretical and practical concepts... It is generally assumed that behavior results from an interaction between susceptible genes and environmental stimuli during critical life stages.The present article reviews the main theoretical and practical concepts in the research of gene environment interaction,emphasizing the need for models simulating real life complexity.We review a novel approach to study gene environment interaction in which a brief post-natal interference with the expression of multiple genes,by hindering the activity of the ubiquitous transcription factor specificity protein 1(Sp1) is followed by later-in-life exposure of rats to stress.Finally,this review discusses the role of peripheral processes in behavioral responses,with the Sp1 model as one example demonstrating how specific behavioral patterns are linked to modulations in both peripheral and central physiological processes.We suggest that models,which take into account the tripartite reciprocal interaction between the central nervous system,peripheral systems and environmental stimuli will advance our understanding of the complexity of behavior. 展开更多
关键词 Gene-environmental interaction SPECIFICITY protein 1 mithramycin Stress animal-model Essential amino acids TRYPTOPHaN Insulin
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Mithramycin inhibits intimal hyperplasia of vein grafts after transplantation of the jugular vein to the abdomainal aorta in rats
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作者 王斌 王新文 段志泉 《Chinese Journal of Traumatology》 CAS 2000年第3期172-175,共4页
Objective: The intimal hyperplasia caused by migration and proliferation of the smooth muscle cells play a most important role in the stenosis of the vein grafts. This study is to explore how the C myc oncogene and it... Objective: The intimal hyperplasia caused by migration and proliferation of the smooth muscle cells play a most important role in the stenosis of the vein grafts. This study is to explore how the C myc oncogene and its protein contribute to the intimal hyperplasia after the jugular vein is transplanted to the abdominal aorta and to assess the effect of Mithramycin on the intimal hyperplasia. Methods: In 60 Wistar rats, a 0.8 cm segment of the right jugular vein graft was interposed at the level of the abdominal aorta. The experiment group received Mithramycin (150 μg/kg IP) 1 h before and after the operation. The control group received normal saline, specimens of vein graft at 2 and 6 h postoperatively were subjected respectively to in situ hybridization. The vein grafts 4 weeks after operation were perfusion fixed. The specimens were stained with hemotoxylin eosin and the computer morphologic analysis system was used to evaluate the degree of intimal thickening. Immunohistochemistry studies of muscle specific α actin, C myc protein and 5 Bromodeoxyuridine were performed. Results: The areas of neointimal and the ratios of neointimal to medial area were significantly smaller and lower in the Mithramycin treated than in the control rats (P< 0.05 ). The 5 Brdu labeling rate between the two groups were also different significantly (P< 0.05 ). Muscle specific α actin showed that the smooth muscle cells formed the most area of myointimal hyperplasia. Steady state C myc mRNA level was increased from 2 h to 6 h postoperatively. The positive rate of the placebo treated group was higher significantly than that of the Mithramycin treated group (P< 0.05 ). Conclusions: Mithramycin may effectively inhibits transcription of C myc in proliferating vascular smooth muscle cells and could be useful in the prevention of restenosis after vascularization. These results support the hypothesis that systemic administration of Mithramycin might immediately prevent intimal proliferation. 展开更多
关键词 Intimal hyperplasia Genes C mye In situ hybridization mithramycin
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Sp1在人肺癌细胞中对survivin表达的调控 被引量:2
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作者 张晓洁 陈余清 李伟 《中国肿瘤》 CAS 2009年第4期319-321,共3页
[目的]探讨Sp1转录因子在人肺腺癌细胞株A549中对survivin基因表达影响。[方法]电泳迁移率分析(EMSA)检测A549细胞核蛋白与标记的survivin启动子序列在有、无mithramycin时的结合情况。用不同浓度mithramycin处理A549细胞,RT-PCR检测sur... [目的]探讨Sp1转录因子在人肺腺癌细胞株A549中对survivin基因表达影响。[方法]电泳迁移率分析(EMSA)检测A549细胞核蛋白与标记的survivin启动子序列在有、无mithramycin时的结合情况。用不同浓度mithramycin处理A549细胞,RT-PCR检测survivin mRNA的表达。[结果]标记的survivin启动子序列-126bp~-106bp与核蛋白作用,出现DNA-核蛋白结合条带,经mithramycin预处理的相同序列出现减弱的DNA-核蛋白结合条带;序列-186bp~-166bp与核蛋白作用后无相应条带。mithramycin使A549细胞survivin mRNA表达显著下降。[结论]survivin启动子-121bp~-116bp处存在Sp1结合位点,mithramycin抑制Sp1与此位点的结合;-178bp~-175bp处可能不存在Sp1结合位点。mithramycin抑制survivin mRNA表达,抑制作用具有浓度依赖性。 展开更多
关键词 肺肿瘤 Sp1转录因子 SURVIVIN mithramycin a549细胞
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