期刊文献+
共找到59篇文章
< 1 2 3 >
每页显示 20 50 100
Spi1 regulates the microglial/macrophage inflammatory response via the PI3K/AKT/mTOR signaling pathway after intracerebral hemorrhage 被引量:1
1
作者 Guoqiang Zhang Jianan Lu +7 位作者 Jingwei Zheng Shuhao Mei Huaming Li Xiaotao Zhang An Ping Shiqi Gao Yuanjian Fang Jun Yu 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第1期161-170,共10页
Preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral hemorrhage.The E26 transformation-specific sequence-related t... Preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral hemorrhage.The E26 transformation-specific sequence-related transcription factor Spi1 regulates microglial/macrophage commitment and maturation.However,the effect of Spi1 on intracerebral hemorrhage remains unclear.In this study,we found that Spi1 may regulate recovery from the neuroinflammation and neurofunctional damage caused by intracerebral hemorrhage by modulating the microglial/macrophage transcriptome.We showed that high Spi1expression in microglia/macrophages after intracerebral hemorrhage is associated with the activation of many pathways that promote phagocytosis,glycolysis,and autophagy,as well as debris clearance and sustained remyelination.Notably,microglia with higher levels of Soil expression were chara cterized by activation of pathways associated with a variety of hemorrhage-related cellular processes,such as complement activation,angiogenesis,and coagulation.In conclusion,our results suggest that Spi1 plays a vital role in the microglial/macrophage inflammatory response following intracerebral hemorrhage.This new insight into the regulation of Spi1 and its target genes may advance our understanding of neuroinflammation in intracerebral hemorrhage and provide therapeutic targets for patients with intracerebral hemorrhage. 展开更多
关键词 intracerebral hemorrhage MACrOPHAGE microglia neuroinflammation PHAGOCYTOSIS pi3k/akt/mTOr signaling pathway Spi1 TrANSCrIPTOMICS
下载PDF
基于IGF-1R/PI3K/AKT的益气固表丸对慢性阻塞性肺疾病模型大鼠的影响及作用机制研究
2
作者 徐丹 荆晶 +4 位作者 李争 王晶 姜敏 王益德 张艳丽 《世界中医药》 CAS 2023年第1期81-86,共6页
目的:益气固表丸对慢性阻塞性肺疾病(COPD)有明显的治疗作用,但具体作用机制尚不清楚。本研究旨在探讨益气固表丸对脂多糖(LPS)联合烟雾暴露构建慢性阻塞性肺病模型大鼠的治疗作用机制。方法:通过大鼠气管内灌注LPS和吸入香烟烟雾构建... 目的:益气固表丸对慢性阻塞性肺疾病(COPD)有明显的治疗作用,但具体作用机制尚不清楚。本研究旨在探讨益气固表丸对脂多糖(LPS)联合烟雾暴露构建慢性阻塞性肺病模型大鼠的治疗作用机制。方法:通过大鼠气管内灌注LPS和吸入香烟烟雾构建慢性阻塞性肺病模型,同时给予模型大鼠低、中、高剂量益气固表丸治疗14 d。观察呼吸参数及肺组织病理变化。采用酶联免疫吸附试验测定支气管肺泡灌洗液(BALF)及血清胰岛素样生长因子1型受体(IGF-1R)、白细胞介素-1β(IL-1β)、IL-10水平。采用蛋白质印迹法检测大鼠肺组织样品中胰岛素样生长因子1受体(IGF-1R)/PI3K/AKT信号通路组分的磷酸化状态。结果:与对照组和低剂量益气组比较,大剂量益气固表丸治疗可显著改善COPD大鼠呼吸参数,减轻肺损伤和炎症,降低BALF和血清炎症介质水平。此外,高剂量益气固表丸干预的COPD大鼠肺组织标本中磷酸化IGF-1R、p-PI3K、p-AKT、p-GSK3、p-mTOR蛋白水平显著降低。结论:益气固表丸对COPD有明显的治疗作用,可能与靶向IGF-1R/PI3K/AKT信号通路有关。 展开更多
关键词 益气固表丸 脂多糖 慢性阻塞性肺疾病 igf-1r/pi3k/akt信号通路 作用机制 胰岛素样生长因子1受体 白细胞介素-1β 白细胞介素-10
下载PDF
Simiao Wan alleviates obesity-associated insulin resistance via PKCε/IRS-1/PI3K/Akt signaling pathway based on network pharmacology analysis and experimental validation
3
作者 Jing Jin Yin-Yue Xu +3 位作者 Wen-Ping Liu Ke-Hua Hu Ning Xue Zu-Guo Zheng 《Traditional Medicine Research》 2023年第10期56-68,共13页
Background:The purpose of the study was to investigatethe active ingredients and potential biochemicalmechanisms of Simiao Wan(SMW)in obesity-associated insulin resistance.Methods:An integrated network pharmacology me... Background:The purpose of the study was to investigatethe active ingredients and potential biochemicalmechanisms of Simiao Wan(SMW)in obesity-associated insulin resistance.Methods:An integrated network pharmacology method to screen the active compoundsand candidate targets,construct the protein-protein-interaction network,and ingredients-targets-pathways network was constructed for topological analysis to identify core targets and main ingredients.To find the possible signaling pathways,enrichment analysis was performed.Further,a model of insulin resistance in HL-7702 cells was established to verify the impact of SMW and the regulatory processes.Results:An overall of 63 active components and 151 candidate targets were obtained,in which flavonoids were the main ingredients.Enrichment analysis indicated that the PI3K-Akt signaling pathway was the potential pathway regulated by SMW in obesity-associated insulin resistance treatment.The result showed that SMW could significantly ameliorate insulin sensitivity,increase glucose synthesis and glucose utilization and reduce intracellular lipids accumulation in hepatocytes.Also,SMW inhibited diacylglycerols accumulation-induced PKCεactivity and decreased its translocation to the membrane.Conclusion:SMW ameliorated obesity-associated insulin resistance through PKCε/IRS-1/PI3K/Akt signaling axis in hepatocytes,providing a new strategy for metabolic disease treatment. 展开更多
关键词 Simiao Wan insulin resistance PkCε/IrS-1/pi3k/akt signaling pathway network pharmacology DAG
下载PDF
IGF1R/PI3K/Akt通路及其调控对非小细胞肺癌血管生成拟态形成影响的研究
4
作者 李荣宾 黄延延 +1 位作者 林贤宾 杨建胜 《福建医药杂志》 CAS 2023年第3期112-115,共4页
目的为非小细胞肺癌(NSCLC)的治疗探索一个潜在的分子靶标.方法通过qPCR、Western blot、免疫组化检测NSCLC组织和癌旁组织KLF16、IGF1R表达情况;通过抑制IGF1R/PI3K/Akt通路活化,检测相关靶标MMP2和MMP9的表达;通过IGF1R/PI3K/Akt通路... 目的为非小细胞肺癌(NSCLC)的治疗探索一个潜在的分子靶标.方法通过qPCR、Western blot、免疫组化检测NSCLC组织和癌旁组织KLF16、IGF1R表达情况;通过抑制IGF1R/PI3K/Akt通路活化,检测相关靶标MMP2和MMP9的表达;通过IGF1R/PI3K/Akt通路抑制剂LY294002干预血管生成拟态(VM)形成.结果与癌旁组织相比,免疫组化、Western blot和qPCR提示,KLF16在NSCLC组织中表达降低,且随着NSCLC级别提高,表达量递减.NSCLC组织中存在明显IGF1R阳性,且IGF1R阳性表达量随着NSCLC级别增高而递增.同时,Western blot和Matrigel三维细胞培养结果表明,随着IGF1R/PI3K/Akt通路抑制剂浓度增加,IGF1R/PI3K/Akt通路相关蛋白质、MMP2、MMP9表达水平也随之降低,肿瘤VM形成随之减少.结论NSCLC VM的形成与IGF1R/PI3K/Akt信号通路有关,KLF16在NSCLC中的表达趋势与IGF1R表达相反,两者之间是否存在调控关系需进一步验证. 展开更多
关键词 非小细胞肺癌 抗血管生成 kLF16 IGF1r/pi3k/akt 血管生成拟态
下载PDF
miR-129-2靶向PIK3R1通过PI3K/AKT信号通路减轻肺内皮细胞损伤 被引量:1
5
作者 袁江汉 郑喜盛 +3 位作者 贾明雅 冯永利 李长力 周发春 《免疫学杂志》 CAS CSCD 北大核心 2023年第7期586-593,共8页
目的探讨miR-129-2在肺血管内皮细胞损伤中的作用及其机制。方法SPF级小鼠40只随机分为对照组、脂多糖(LPS)组、空载组、过表达组,给予气管滴注LPS诱导急性肺损伤(ALI),尾静脉注射高表达慢病毒来过表达miR-129-2,观察ALI小鼠呼吸频率、... 目的探讨miR-129-2在肺血管内皮细胞损伤中的作用及其机制。方法SPF级小鼠40只随机分为对照组、脂多糖(LPS)组、空载组、过表达组,给予气管滴注LPS诱导急性肺损伤(ALI),尾静脉注射高表达慢病毒来过表达miR-129-2,观察ALI小鼠呼吸频率、体质量等一般情况,检测miR-129-2及炎症因子IL-6、IL-10、TNF-α表达水平和肺损伤程度。人肺微血管内皮细胞(HPMECs)分为Control组、LPS组、NC组和mimic组,LPS处理诱导细胞损伤,转染miR-129-2 mimic来上调miR-129-2的水平,划痕实验及Transwell实验检测细胞迁移能力,检测各组细胞中miR-129-2、IL-6、IL-10、TNF-α及PIK3R1 mRNA的表达水平。双荧光素酶实验验证miR-129-2与PIK3R1的靶向关系,Western blot检测miR-129-2对PIK3R1及PI3K/AKT信号通路蛋白表达的影响。结果在小鼠中,miR-129-2过表达能使小鼠进食增加、呼吸频率减慢、体质量增加、肺组织损伤减轻,IL-6、TNF-α表达降低,IL-10表达升高(P<0.05)。在HPMECs中,mimic转染使miR-129-2表达水平上调,炎症因子表达水平降低,细胞迁移能力增强,PIK3R1表达降低(P<0.05);双荧光素酶报告显示miR-129-2与PIK3R1存在结合位点,miR-129-2下调使PIK3R1表达增加,PI3K/AKT信号通路被激活。结论miR-129-2过表达能够减轻小鼠炎症反应和肺损伤,并能介导PIK3R1通过PI3K/AKT信号通路缓解肺内皮细胞损伤。 展开更多
关键词 mir-129-2 pik3r1 pi3k/akt 内皮细胞损伤 炎症因子
下载PDF
基于IGF-1/PI3K/Akt信号通路探讨象皮生肌膏对压力性损伤大鼠模型的影响及机制研究 被引量:2
6
作者 郭李梦 彭露 +2 位作者 高子琪 刘彬 廖若夷 《湖南中医药大学学报》 CAS 2023年第9期1547-1552,共6页
目的通过动物实验观察并基于类胰岛素一号生长因子(insulin-like growth factors-1,IGF-1)/磷脂酰肌醇3激酶(phosphoinositide3-kinase,PI3K)/蛋白激酶B(protein kinase B,Akt)信号通路探讨象皮生肌膏对压力性损伤大鼠模型的影响。方法... 目的通过动物实验观察并基于类胰岛素一号生长因子(insulin-like growth factors-1,IGF-1)/磷脂酰肌醇3激酶(phosphoinositide3-kinase,PI3K)/蛋白激酶B(protein kinase B,Akt)信号通路探讨象皮生肌膏对压力性损伤大鼠模型的影响。方法将40只SD大鼠(SPF级,雌雄各半)复制压力性损伤大鼠模型,造模成功后随机均分为模型组(生理盐水纱布外敷)、阳性对照组(三乙醇胺乳膏外用)、象皮生肌组(象皮生肌膏外用)、联合给药组(三乙醇胺乳膏与象皮生肌膏联合外用)。另取10只健康SD大鼠作为空白组,仅同部位置入磁性装置,不予施加压力。实验过程中,每天记录各组大鼠愈合情况。实验结束时,HE染色法观察创面病理性损伤情况,ELISA法检测血清肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-1β(interleukin-1β,IL-1β)、白细胞介素-6(interleukin-6,IL-6)水平,Western blot法及RT-PCR法检测创面组织中PI3K、Akt、哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)、IGF-1蛋白及mRNA的表达情况。结果与空白组比较,模型组大鼠创面面积明显增大(P<0.05);与模型组比较,阳性对照组、象皮生肌组、联合给药组大鼠的创面面积均减小(P<0.05);与阳性对照组及象皮生肌组比较,联合给药组创面面积缩小(P<0.05)。HE染色结果显示,空白组大鼠创面病理结构较完整,组织细胞排列较规则且病理致密,未见明显组织坏死碎片、水肿及炎性浸润;模型组可见明显的肌肉纤维坏死碎片,空泡变性,纤维肿大、横断;阳性对照组、象皮生肌组、联合给药组可见不同程度的病理缓解。与空白组比较,模型组大鼠血清炎性因子TNF-α、IL-1β、IL-6水平明显升高(P<0.05),PI3K、Akt、mTOR、IGF-1蛋白及mRNA表达明显升高(P<0.05);与模型组比较,阳性对照组、象皮生肌组、联合给药组大鼠血清炎性因子TNF-α、IL-1β、IL-6水平显著降低(P<0.05),PI3K、Akt、mTOR、IGF-1蛋白及mRNA表达显著升高(P<0.05);与阳性对照组及象皮生肌组比较,联合给药组血清炎性因子TNF-α、IL-1β、IL-6水平以及PI3K、Akt、mTOR、IGF-1蛋白及mRNA表达水平明显降低(P<0.05)。结论象皮生肌膏可改善压力性损伤大鼠模型创面病理情况,可能与象皮生肌膏上调IGF-1/PI3K/Akt信号通路相关蛋白表达,抑制炎性因子表达相关。 展开更多
关键词 压力性损伤 象皮生肌膏 igf-1/pi3k/akt信号通路 血清炎性因子 机制研究
下载PDF
裸花紫珠调控IGF-1/PI3K/Akt信号通路对糖尿病足溃疡大鼠创面愈合的影响 被引量:2
7
作者 李吉庆 林道斌 +1 位作者 张永杰 陈学武 《中国老年学杂志》 CAS 北大核心 2023年第6期1458-1462,共5页
目的 探讨裸花紫珠调控胰岛素样生长因子(IGF)-1/磷脂酰肌醇-3激酶(PI3K)/蛋白激酶B(Akt)信号通路对糖尿病足溃疡(DFU)大鼠创面愈合的影响。方法 采用高脂高糖饲料联合腹腔注射链脲佐菌素建立糖尿病(DM)模型大鼠,再用DM大鼠和正常大鼠... 目的 探讨裸花紫珠调控胰岛素样生长因子(IGF)-1/磷脂酰肌醇-3激酶(PI3K)/蛋白激酶B(Akt)信号通路对糖尿病足溃疡(DFU)大鼠创面愈合的影响。方法 采用高脂高糖饲料联合腹腔注射链脲佐菌素建立糖尿病(DM)模型大鼠,再用DM大鼠和正常大鼠构建溃疡模型,可分为正常组、模型组、凡士林纱布组、裸花紫珠组,每组12只。正常组和模型组均用生理盐水纱布外敷,凡士林纱布组(10 mg/kg),裸花紫珠组(20 mg/kg)。采用Photoshop软件测算大鼠创面愈合率,光学显微镜观察创缘组织结构变化。利用实时荧光定量聚合酶链式反应(RT-PCR)检测创面组织IGF-1、IGF-1受体(IGF-1R)、PI3K、Akt、一氧化氮合酶(eNOS)、血管内皮细胞生长因子(VEGF)、VEGF受体(VEGFR)2的基因表达水平;并用Western印迹检测各组组织中IGF-1、IGF-1R、PI3K、Akt、eNOS、VEGF、VEGFR2蛋白表达水平。结果 治疗后第3、7天,与模型组比较,凡士林纱布组、裸花紫珠组创面愈合率显著升高,且治疗第7天裸花紫珠组和正常组显著高于凡士林纱布组(P<0.05);病理结果显示,除模型组外,各组毛细血管、炎症细胞、纤维细胞生长均明显增加;RT-PCR检测提示,正常组、凡士林纱布组及裸花紫珠组创面组织中IGF-1、IGF-1R、PI3K、Akt、eNOS、VEGF、VEGFR2 mRNA及蛋白表达均较模型组明显升高,且正常组及裸花紫珠组明显高于凡士林纱布组(P<0.05)。结论 裸花紫珠能有效促进DFU大鼠创面愈合,并可能通过IGF-1/PI3K/Akt信号通路发挥治疗作用。 展开更多
关键词 裸花紫珠 糖尿病足溃疡模型 胰岛素样生长因子(igf-1)/磷脂酰肌醇-3激酶(pi3k)/蛋白激酶B(akt)信号通路
下载PDF
IGF-1对Rh1肉瘤细胞PI3K/Akt/mTOR信号通路的影响
8
作者 金家红 黄文峰 《中国老年学杂志》 CAS CSCD 北大核心 2011年第22期4384-4385,共2页
目的探讨胰岛素样生长因子(IGF)1对Rh1肉瘤细胞生长活性和PI3K/Akt/mTOR信号通路的背景变化。方法常规细胞培养,用无血清培养基消除内源性因子影响27 h,再用IGF-1(终浓度为10 ng/ml)刺激72 h,流式细胞仪检测细胞生长活性;另外Western印... 目的探讨胰岛素样生长因子(IGF)1对Rh1肉瘤细胞生长活性和PI3K/Akt/mTOR信号通路的背景变化。方法常规细胞培养,用无血清培养基消除内源性因子影响27 h,再用IGF-1(终浓度为10 ng/ml)刺激72 h,流式细胞仪检测细胞生长活性;另外Western印迹方法观察IGF-1刺激细胞5、10、20、30和60 min后Akt(s473)、S6的动态变化。结果与对照组相比,IGF-1可促进Rh1细胞存活。IGF-1刺激不同时间后S6磷酸化则随着时间的延长逐渐增强;IGF-1亦导致Akt(s473)位点的磷酸化,随时间的延长,磷酸化Akt在5 min时达高峰,此后逐渐减弱。结论Akt、S6等是PI3K/Akt/mTOR信号通路中的重要信号分子,对Rh1细胞而言,在IGF-1刺激下S6有逐渐增强的变化,Akt(s473)位点磷酸化则有减弱的动态变化。 展开更多
关键词 igf-1 pi3k/akt/MTOr
下载PDF
Fibroblast-derived CXCL12/SDF-1α promotes CXCL6 secretion and co-operatively enhances metastatic potential through the PI3K/Akt/m TOR pathway in colon cancer 被引量:12
9
作者 Jia-Chi Ma Xiao-Wen Sun +8 位作者 He Su Quan Chen Tian-Kang Guo Yuan Li Xiao-Chang Chen Jin Guo Zhen-Qiang Gong Xiao-Dan Zhao Jian-Bo Qi 《World Journal of Gastroenterology》 SCIE CAS 2017年第28期5167-5178,共12页
AIM To investigate the underlying mechanism by which CXCL12 and CXCL6 influences the metastatic potential of colon cancer and internal relation of colon cancer and stromal cells. METHODS Western blotting was used to d... AIM To investigate the underlying mechanism by which CXCL12 and CXCL6 influences the metastatic potential of colon cancer and internal relation of colon cancer and stromal cells. METHODS Western blotting was used to detect the expression of CXCL12 and CXCL6 in colon cancer cells and stromal cells. The co-operative effects of CXCL12 and CXCL6 on proliferation and invasion of colon cancer cells and human umbilical vein endothelial cells(HUVECs) were determined by enzyme-linked immunosorbent assay,and proliferation and invasion assays. The angiogenesis of HUVECs through interaction with cancer cells and stromal cells was examined by angiogenesis assay. We eventually investigated activation of PI3K/Akt/m TOR signaling by CXCL12 involved in the metastatic process of colon cancer.RESULTS CXCL12 was expressed in DLD-1 cancer cells and fibroblasts. The secretion level of CXCL6 by colon cancer cells and HUVECs were significantly promoted by fibroblasts derived from CXCL12. CXCL6 and CXCL2 could significantly enhance HUVEC proliferation and migration(P < 0.01). CXCL6 and CXCL2 enhanced angiogenesis by HUVECs when cultured with fibroblast cells and colon cancer cells(P < 0.01). CXCL12 also enhanced the invasion of colon cancer cells. Stromal cell-derived CXCL12 promoted the secretion level of CXCL6 and co-operatively promoted metastasis of colon carcinoma through activation of the PI3K/Akt/m TOR pathway.CONCLUSION Fibroblast-derived CXCL12 enhanced the CXCL6 secretion of colon cancer cells,and both CXCL12 and CXCL6 co-operatively regulated the metastasis via the PI3K/Akt/m TOR signaling pathway. Blocking this pathway may be a potential anti-metastatic therapeutic target for patients with colon cancer. 展开更多
关键词 CXCL12/SDF-1α CXCL6 Metastasis pi3k/akt/m TOr pathway Colon cancer
下载PDF
shRNA-interfering LSD1 inhibits proliferation and invasion of gastric cancer cells via VEGF-C/PI3K/AKT signaling pathway 被引量:7
10
作者 Hong-Ming Pan Wei-Ya Lang +2 位作者 Li-Jie Yao Yan Wang Xiao-Ling Li 《World Journal of Gastrointestinal Oncology》 SCIE CAS 2019年第8期622-633,共12页
BACKGROUND Histone Lysine Specific Demethylase 1(LSD1)is the first histone demethylase to be discovered,which regulates various biological functions by making lysine of histone H3K4,H3K9 and non-histone substrates dem... BACKGROUND Histone Lysine Specific Demethylase 1(LSD1)is the first histone demethylase to be discovered,which regulates various biological functions by making lysine of histone H3K4,H3K9 and non-histone substrates demethylated.Abnormal regulation of LSD1 is closely related to the occurrence and development of gastric cancer.The change of LSD1 expression level plays an important role in the proliferation and metastasis of gastric cancer cells.The study of its function and mechanism may provide a theoretical basis for early diagnosis and targeted therapy of gastric cancer.AIM To investigate the effect of downregulation of lysine-specific demethylase 1(LSD1)expression on proliferation and invasion of gastric cancer cells and the possible regulatory mechanisms of the VEGF-C/PI3K/AKT signaling pathway.METHODS The LSD1-specific short hairpin RNA(shRNA)interference plasmid was transiently transfected,and expression of LSD1 was downregulated.The cell proliferation ability of LSD1 was observed by CCK-8 assay after downregulating expression of LSD1.Transwell invasion assay was used to observe the change of cell invasion ability after downregulating expression of LSD1.Expression of phosphorylated phosphoinositide 3-kinase(p-PI3K),PI3K,p-AKT,AKT,vascular endothelial growth factor receptor(VEGFR)-3,matrix metalloproteinase(MMP)-2 and MMP-9 in each group was detected by Western blotting.RESULTS The cell proliferation ability of transiently transfected LSD1-shRNA interference plasmid group was significantly lower than that of the control group(P<0.05).Transwell invasion assay showed that the number of cells across the membrane of the LSD1-shRNA transfection group(238.451±5.216)was significantly lower than that of the control group(49.268±6.984)(P<0.01).Western blotting showed that expression level of VEGF-C,p-PI3K,PI3K,p-AKT,AKT,VEGFR-3,MMP-2 and MMP-9 in the LSD1-shRNA group was significantly lower than that in the control group(P<0.05).CONCLUSION Downregulation of LSD1 expression inhibits metastatic potential of gastric cancer cells,and VEGF-C-mediated activation of PI3K/AKT signaling pathway,which may be an important mechanism for inhibiting lymph node metastasis in gastric cancer cells. 展开更多
关键词 Gastric cancer Lysine specific histone DEMETHYLASE 1 CELL PrOLIFErATION CELL INVASION VEGF-C/pi3k/akt signaling pathway
下载PDF
TBL1XR1 induces cell proliferation and inhibit cell apoptosis by the PI3K/AKT pathway in pancreatic ductal adenocarcinoma 被引量:6
11
作者 Jian-Feng Gu Wei Fu +4 位作者 Hai-Xin Qian Wen-Xiu Gu Yang Zong Qian Chen Long Lu 《World Journal of Gastroenterology》 SCIE CAS 2020年第25期3586-3602,共17页
BACKGROUND Pancreatic ductal adenocarcinoma(PDAC) is one of the deadliest solid tumors. Identification of diagnostic and therapeutic biomarkers for PDAC is urgently needed. Transducin(β)-like 1 X-linked receptor 1(TB... BACKGROUND Pancreatic ductal adenocarcinoma(PDAC) is one of the deadliest solid tumors. Identification of diagnostic and therapeutic biomarkers for PDAC is urgently needed. Transducin(β)-like 1 X-linked receptor 1(TBL1 XR1) has been linked to the progression of various human cancers. Nevertheless, the function and role of TBL1 XR1 in pancreatic cancers are unclear.AIM To elucidate the function and potential mechanism of TBL1 XR1 in the development of PDAC.METHODS Ninety patients with histologically-confirmed PDAC were included in this study. PDAC tumor samples and cell lines were used to determine the expression of TBL1 XR1. CCK-8 assays and colony formation assays were carried out to assess PDAC cell viability. Flow cytometry was performed to measure the changes in the cell cycle and cell apoptosis. Changes in related protein expression were measured by western blot analysis. Animal analysis was conducted to confirm the impact of TBL1 XR1 in vivo.RESULTS Patients with TBL1 XR1-positive tumors had worse overall survival than those with TBL1 XR1-negative tumors. Moreover, we found that TBL1 XR1 strongly promoted PDAC cell proliferation and inhibited PDAC cell apoptosis. Moreover, knockdown of TBL1 XR1 induced G0/G1 phase arrest. In vivo animal studies confirmed that TBL1 XR1 accelerated tumor cell growth. The results of western blot analysis showed that TBL1 XR1 might play a key role in regulating PDAC cell proliferation and apoptosis via the PI3 K/AKT pathway.CONCLUSION TBL1 XR1 promoted PDAC cell progression and might be an effective diagnostic and therapeutic marker for pancreatic cancer. 展开更多
关键词 Pancreatic ductal adenocarcinoma TBL1Xr1 PrOLIFErATION pi3k/akt pathway
下载PDF
EMP-1 Promotes Tumorigenesis of NSCLC through PI3K/AKT Pathway 被引量:2
12
作者 来森艳 王桂华 +3 位作者 曹小年 李兆明 胡俊波 王晶 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2012年第6期834-838,共5页
This study examined the role of EMP-1 in tumorigenesis of non-small cell lung carcinoma (NSCLC) and the possible mechanism. Specimens were collected from 28 patients with benign lung diseases and 28 with NSCLC, and im... This study examined the role of EMP-1 in tumorigenesis of non-small cell lung carcinoma (NSCLC) and the possible mechanism. Specimens were collected from 28 patients with benign lung diseases and 28 with NSCLC, and immunohis to chemically detected to evaluate the correlation of EMP-1 expression to the clinical features of NSCLC. Recombinant adenovirus was constructed to over-express EMP-1 and then infect PC9 cells. Cell proliferation was measured by Ki67 staining. Western blotting was performed to examine the effect of EMP-1 on the PI3K/AKT signaling. Moreover, tumor xeno-grafts were established by subcutaneous injection of PC9 cell suspension (about 5×107/mL in 100 μL of PBS) into the right hind limbs of athymic nude mice. The results showed EMP-1 was significantly up-regulated in NSCLC patients as compared with those with benign lung diseases. Over-expression of EMP-1 promoted proliferation of PC9 cells, which coincided with the activation of the PI3K/AKT pathway. EMP-1 promoted the growth of xenografts of PC9 cells in athymic nude mice. It was concluded that EMP-1 expression may contribute to the development and progress of NSCLC by activating PI3K/AKT pathway. 展开更多
关键词 NSCLC EMP-1 gene pi3k/akt pathway TUMOrIGENESIS
下载PDF
miR-155靶向调节PIK3R1对类风湿关节炎大鼠模型PI3K/Akt/mTOR信号通路的影响 被引量:4
13
作者 吴焘 张国秋 +1 位作者 李超 张兰涛 《中国骨质疏松杂志》 CAS CSCD 北大核心 2022年第11期1593-1598,共6页
目的 探讨miR-155靶向调节PIK3R1对类风湿关节炎(rheumatoid arthritis, RA)大鼠PI3K/Akt/mTOR信号通路的影响。方法 SD大鼠随机分为对照组、模型组、miR-155 agomir组、miR-155 antagomir组、miR-155阴性对照组,诱导RA模型,分组处理后... 目的 探讨miR-155靶向调节PIK3R1对类风湿关节炎(rheumatoid arthritis, RA)大鼠PI3K/Akt/mTOR信号通路的影响。方法 SD大鼠随机分为对照组、模型组、miR-155 agomir组、miR-155 antagomir组、miR-155阴性对照组,诱导RA模型,分组处理后,观察关节症状,检测关节炎指数及后足趾容积;HE染色观察大鼠关节组织病理形态;使用试剂盒检测大鼠关节组织炎性因子IL-6、IL-17及IL-18水平;免疫印迹检测大鼠关节组织PI3K/Akt/mTOR信号通路蛋白表达;qRT-PCR实验检测大鼠关节组织miR-155及PIK3R1 mRNA水平;双荧光素酶报告基因实验检测miR-155对PIK3R1的靶向调控作用。结果 与对照组比较,模型组大鼠关节炎症状明显,关节炎指数、后足趾容积、关节组织炎性因子IL-6、IL-17及IL-18水平、关节组织p-PI3K/PI3K、p-Akt/Akt及p-mTOR/mTOR水平、关节组织miR-155水平明显升高(P<0.05),PIK3R1 mRNA水平明显降低(P<0.05)。与模型组、miR-155阴性对照组比较,miR-155 antagomir组大鼠上述指标得到明显改善(P<0.05);miR-155 agomir组与miR-155 antagomir组趋势相反(P<0.05)。结论 miR-155可靶向下调PIK3R1的表达,激活PI3K/Akt/mTOR信号,加重RA大鼠关节炎症损伤,下调miR-155表达,可抑制PI3K/Akt/mTOR信号激活及炎症反应发生发展,改善关节炎症状。 展开更多
关键词 MIr-155 pik3r1 类风湿关节炎 pi3k/akt/MTOr 大鼠
下载PDF
PI3K、ERK、IGF-1R和ER蛋白在宫颈癌细胞株中的表达及意义 被引量:3
14
作者 宁超 荣小灵 杜靖 《新疆医科大学学报》 CAS 2016年第8期1044-1047,共4页
目的研究体外特定细胞株(C33a、HaCaT及SiHa)中磷酸肌醇3激酶(PI3K)、细胞外调节激酶(ERK)、胰岛素样生长因子-1受体(IGF-1R)和雌激素受体(ER)蛋白的表达量,分析各蛋白的表达与HPV16感染致癌的关系。方法培养C33a、HaCaT及SiHa 3种细胞... 目的研究体外特定细胞株(C33a、HaCaT及SiHa)中磷酸肌醇3激酶(PI3K)、细胞外调节激酶(ERK)、胰岛素样生长因子-1受体(IGF-1R)和雌激素受体(ER)蛋白的表达量,分析各蛋白的表达与HPV16感染致癌的关系。方法培养C33a、HaCaT及SiHa 3种细胞,采用蛋白免疫印迹(Western blot)技术检测IGF-1R、PI3K、ERK和ER蛋白在3种细胞株中的表达水平。结果 IGF-1R、PI3K和ERK蛋白在SiHa细胞株中的表达高于在C33a、HaCaT细胞株中的表达,差异有统计学意义(P<0.05),而在SiHa细胞株中ER的表达低于在C33a细胞株中的表达,差异有统计学意义(P<0.05)。结论 PI3K、ERK、IGF-1R和ER蛋白在宫颈癌细胞株中呈现不同程度的表达,可能与HPV16感染后宫颈癌变存在一定的关系。 展开更多
关键词 宫颈癌细胞 pi3k Erk igf-1r Er
下载PDF
The basic helix-loop-helix(bHLH)transcription factor,DEC1,provides neuroprotection from apoptosis induced by MPP^+ through PI3K/Akt pathway in SHSY5Y cells
15
作者 ZHU Zhu WANG Yu-wen YANG Jian 《中国药理学与毒理学杂志》 CAS CSCD 北大核心 2016年第10期1027-1027,共1页
OBJECTIVE To determine the role of the basic helix-loop-helix(b HLH)transcription factor,differentiated embryonic chondrocyte gene 1(DEC1),in the apoptosis induced by 1-methyl-4-phenylpyridiniumion(MPP+)in SH-SY5Y cel... OBJECTIVE To determine the role of the basic helix-loop-helix(b HLH)transcription factor,differentiated embryonic chondrocyte gene 1(DEC1),in the apoptosis induced by 1-methyl-4-phenylpyridiniumion(MPP+)in SH-SY5Y cells.METHODS SH-SY5Y cells were treated with different concentrations of MPP+for 24or 48 h.The cell inhibition and apoptosis were measured by MTT and DAPI staining.DEC1,the apoptosis-related proteins and PI3K/Akt/GSK3β/β-catenin signaling were determined by Western blotting.The expression of DEC1was regulated by overexpression and sh RNA.RESULTS MPP+induces apoptosis along with decreasing of DEC1expression in SH-SY5Y cells.Overexpression or knockdown of DEC1 can alleviate or enhance the cell inhibition induced by MPP+.And overexpression of DEC1 can alleviate the increased cleaved caspase 3/caspase 3 but not alleviate Bax/Bcl-2 induced by MPP+.Meanwhile,MPP+represses PI3Kp110α,p-Akt/Akt,p-GSK-3β/GSK-3βandβ-catenin expression,which is accompanied by decreasing DEC1 expressions.It is confirmed that the activator or inhibitor of PI3K/Akt/GSK-3βpathway can alleviate or enhance the repression of PI3K/Akt/GSK3β/β-catenin signaling cascade induced by MPP+.Further study,we find that overexpression of DEC1 alone can increase PI3Kp110α,p-Akt/Akt,p-GSK-3β/GSK-3β,andβ-catenin expression.More importantly,overexpression of DEC1 significantly alleviates the decreased levels of PI3Kp110α,p-Akt/Akt,p-GSK-3β/GSK-3β,andβ-catenin induced by MPP+.CONCLUSION DEC1 provides neuroprotection from apoptosis induced by MPP+through PI3K/Akt pathway in SH-SY5Y cells.Promisingly,DEC1 is a candidate gene that may provide a novel therapeutic approach for the treatment of Parkinson disease. 展开更多
关键词 differentiated embryonic chondrocyte gene 1 1-methyl-4-phenylpyridiniumion NEUrOPrOTECTION pi3k/akt pathway
下载PDF
三七皂苷R1调控PI3K/AKT/mTOR信号通路诱导人下咽鳞状细胞癌FaDu细胞凋亡和自噬 被引量:7
16
作者 高鑫 樊新龙 +4 位作者 曾巍 梁冀望 郭囡 杨骁 赵月皎 《现代肿瘤医学》 CAS 北大核心 2022年第13期2311-2314,共4页
目的:探讨三七皂苷R1(notoginsenoside R1,NGR1)对人下咽鳞状细胞癌(hypopharyngeal squamous cell carcinoma,HSCC)FaDu细胞凋亡以及自噬的影响,并对其涉及的信号通路进行研究。方法:75μmol/L、150μmol/L、300μmol/L NGR1作用于FaD... 目的:探讨三七皂苷R1(notoginsenoside R1,NGR1)对人下咽鳞状细胞癌(hypopharyngeal squamous cell carcinoma,HSCC)FaDu细胞凋亡以及自噬的影响,并对其涉及的信号通路进行研究。方法:75μmol/L、150μmol/L、300μmol/L NGR1作用于FaDu细胞24 h后,采用MTT检测细胞增殖能力;流式细胞术检测细胞凋亡;自噬双标腺病毒检测自噬流;Western blot检测自噬相关蛋白LC3Ⅱ/LC3Ⅰ以及PI3K/AKT/mTOR信号通路相关蛋白表达水平。结果:NGR1能够抑制FaDu细胞的增殖并促进细胞凋亡;NGR1可诱导FaDu细胞自噬,并呈一定浓度依赖性;Western blot结果显示,NGR1作用于Fa Du细胞24 h后,LC3Ⅱ表达明显增加,而p-PI3K、p-AKT、p-m TOR表达相较于Control组明显下降。结论:NGR1可抑制Fa Du细胞增殖,诱导细胞凋亡与自噬,其机制可能与抑制PI3K/AKT/m TOR信号通路有关。 展开更多
关键词 下咽鳞状细胞癌 FaDu细胞 三七皂苷r1 凋亡 自噬 pi3k/akt/MTOr
下载PDF
Eukaryotic elongation factor-1α 2 knockdown inhibits hepatocarcinogenesis by suppressing PI3K/Akt/NF-κB signaling 被引量:8
17
作者 Fu-Nan Qiu Yi Huang +4 位作者 Dun-Yan Chen Feng Li Yan-An Wu Wen-Bing Wu Xiao-Li Huang 《World Journal of Gastroenterology》 SCIE CAS 2016年第16期4226-4237,共12页
AIM: To assess the impact of eukaryotic elongation factor 1 alpha 2 (eEF1A2) on hepatocellular carcinoma (HCC) cell proliferation, apoptosis, migration and invasion, and determine the underlying mechanisms.METHODS: eE... AIM: To assess the impact of eukaryotic elongation factor 1 alpha 2 (eEF1A2) on hepatocellular carcinoma (HCC) cell proliferation, apoptosis, migration and invasion, and determine the underlying mechanisms.METHODS: eEF1A2 levels were detected in 62 HCC tissue samples and paired pericarcinomatous specimens, and the human HCC cell lines SK-HEP-1, HepG2 and BEF-7402, by real-time PCR and immunohistochemistry. Experimental groups included eEF1A2 silencing in BEL-7402 cells with lentivirus eEF1A2-shRNA (KD group) and eEF1A2 overexpression in SK-HEP-1 cells with eEF1A2 plasmid (OE group). Non-transfected cells (control group) and lentivirus-based empty vector transfected cells (NC group) were considered control groups. Cell proliferation (MTT and colony formation assays), apoptosis (Annexin V-APC assay), cell cycle (DNA ploidy assay), and migration and invasion (Transwell assays) were assessed. Protein levels of PI3K/Akt/NF-&#x003ba;B signaling effectors were evaluated by Western blot.RESULTS: eEF1A2 mRNA and protein levels were significantly higher in HCC cancer tissue samples than in paired pericarcinomatous and normal specimens. SK-HEP-1 cells showed lower eEF1A2 mRNA levels; HepG2 and BEL-7402 cells showed higher eEF1A2 mRNA levels, with BEL-7402 cells displaying the highest amount. Efficient eEF1A2 silencing resulted in reduced cell proliferation, migration and invasion, increased apoptosis, and induced cell cycle arrest. The PI3K/Akt/NF-&#x003ba;B signaling pathway was notably inhibited. Inversely, eEF1A2 overexpression resulted in promoted cell proliferation, migration and invasion.CONCLUSION: eEF1A2, highly expressed in HCC, is a potential oncogene. Its silencing significantly decreases HCC tumorigenesis, likely by inhibiting PI3K/Akt/NF-&#x003ba;B signaling. 展开更多
关键词 Hepatocellular carcinoma CArCINOGENESIS Eukaryotic elongation factor 1 alpha 2 Proliferation pi3k/akt/NF-�3ba B signaling pathway
下载PDF
Scoparone inhibits pancreatic cancer through PI3K/Akt signaling pathway 被引量:6
18
作者 Na Li Fan Yang +3 位作者 Dong-Yan Liu Jin-Tao Guo Nan Ge Si-Yu Sun 《World Journal of Gastrointestinal Oncology》 SCIE 2021年第9期1164-1183,共20页
BACKGROUND Pancreatic cancer is a highly malignant tumor of the gastrointestinal system whose emerging resistance to chemotherapy has necessitated the development of novel antitumor treatments.Scoparone,a traditional ... BACKGROUND Pancreatic cancer is a highly malignant tumor of the gastrointestinal system whose emerging resistance to chemotherapy has necessitated the development of novel antitumor treatments.Scoparone,a traditional Chinese medicine monomer with a wide range of pharmacological properties,has attracted considerable attention for its antitumor activity.AIM To explore the potential antitumor effect of scoparone on pancreatic cancer and the possible molecular mechanism of action.METHODS The target genes of scoparone were determined using both the bioinformatics and multiplatform analyses.The effect of scoparone on pancreatic cancer cell proliferation,migration,invasion,cell cycle,and apoptosis was detected in vitro.The expression of hub genes was tested using quantitative reverse transcription polymerase chain reaction(qRT-PCR),and the molecular mechanism was analyzed using Western blot.The in vivo effect of scoparone on pancreatic cancer cell proliferation was detected using a xenograft tumor model in nude mice as well as immunohistochemistry.RESULTS The hub genes involved in the suppression of pancreatic cancer by scoparone were obtained by network bioinformatics analyses using publicly available databases and platforms,including SwissTargetPrediction,STITCH,GeneCards,CTD,STRING,WebGestalt,Cytoscape,and Gepia;AKT1 was confirmed using qRT-PCR to be the hub gene.Cell Counting Kit-8 assay revealed that the viability of Capan-2 and SW1990 cells was significantly reduced by scoparone treatment exhibiting IC50 values of 225.2μmol/L and 209.1μmol/L,respectively.Wound healing and transwell assays showed that scoparone inhibited the migration and invasion of pancreatic cancer cells.Additionally,flow cytometry confirmed that scoparone caused cell cycle arrest and induced apoptosis.Scoparone also increased the expression levels of Bax and cleaved caspase-3,decreased the levels of MMP9 and Bcl-2,and suppressed the phosphorylation of Akt without affecting total PI3K and Akt.Moreover,compared with the control group,xenograft tumors,in the 200μmol/L scoparone treatment group,were smaller in volume and lighter in weight,and the percentages of Ki65-and PCNA-positive cells were decreased.CONCLUSION Our findings indicate that scoparone inhibits pancreatic cancer cell proliferation in vitro and in vivo,inhibits migration and invasion,and induces cycle arrest and apoptosis in vitro through the PI3K/Akt signaling pathway. 展开更多
关键词 Pancreatic cancer SCOPArONE akt1 pi3k/akt signaling pathway Bioinformatics analysis Xenograft tumor
下载PDF
PI3K/AKT/GSK3β信号通路参与腺苷A1R介导异丙酚对缺血再灌注损伤大鼠的脑保护作用 被引量:6
19
作者 夏洪莲 钟微微 +3 位作者 金鹏 陈猛 刘再英 张艳丽 《中国临床药理学与治疗学》 CAS CSCD 2020年第12期1344-1350,共7页
目的:探讨PI3K/AKT/GSK-3β信号通路参与异丙酚对缺血再灌注损伤大鼠的脑保护作用及机制。方法:健康雄性SD大鼠72只,所有大鼠参照Zea Longa法建立局灶性脑缺血再灌注损伤的模型。随机分成6组(n=12),A-假手术组,B-模型组(MCAO),C-异丙酚... 目的:探讨PI3K/AKT/GSK-3β信号通路参与异丙酚对缺血再灌注损伤大鼠的脑保护作用及机制。方法:健康雄性SD大鼠72只,所有大鼠参照Zea Longa法建立局灶性脑缺血再灌注损伤的模型。随机分成6组(n=12),A-假手术组,B-模型组(MCAO),C-异丙酚组,D-异丙酚+腺苷A1R拮抗剂组(DPCPX),E-异丙酚组+PI3K特异性抑制剂(LY294002),F-异丙酚+GSK-3β抑制剂组(SB216763),观察大鼠术后24 h神经功能评分情况;LDF监测插栓前后脑血流变化;采用TTC染色法检测各组大鼠的脑梗死体积;用HE染色方法观察大鼠脑组织形态学改变;免疫组织化学法检测Bcl-2阳性细胞表达;采用TUNEL检测各组大脑脑皮质缺血周围神经元凋亡细胞的百分率。结果:与A组比较,B、C、D、E及F组大鼠行为学、脑梗死体积、细胞凋亡率、Bcl-2蛋白表达量均增加(P<0.05);与C组比较,B、D、E组大鼠行为学评分,脑梗死体积及细胞凋亡率均明显增加,Bcl-2蛋白表达量均明显减少(P<0.01),F组Bcl-2蛋白表达量却增加,细胞凋亡率降低(P<0.05),行为学评分减少、梗死体积减少(P<0.05)。结论:腺苷A1R介导的异丙酚对缺血再灌注损伤大鼠的神经保护作用可能与PI3K/AKT/GSK-3β信号转导通路有关。 展开更多
关键词 pi3k/akt/GSk-3β信号通路 腺苷A1r 异丙酚 缺血再灌注
下载PDF
冲击波对大鼠骨骼肌钝挫伤修复及IGF-1/PI3K/AKT信号通路的影响 被引量:4
20
作者 吕欣 曹宇 周达岸 《中国运动医学杂志》 CAS CSCD 北大核心 2020年第12期953-958,987,共7页
目的:探讨冲击波对大鼠骨骼肌钝挫伤的修复作用及IGF-1/PI3K/AKT信号通路的影响,为探索冲击波对骨骼肌损伤修复的作用机制提供依据。方法:随机数字表法将21只雄性成年SD大鼠分为正常组、模型组和治疗组,后两组利用自制重物打击装置造模... 目的:探讨冲击波对大鼠骨骼肌钝挫伤的修复作用及IGF-1/PI3K/AKT信号通路的影响,为探索冲击波对骨骼肌损伤修复的作用机制提供依据。方法:随机数字表法将21只雄性成年SD大鼠分为正常组、模型组和治疗组,后两组利用自制重物打击装置造模。采用作用参数为0.14 mJ/mm2、10 Hz的冲击波于造模后24 h作用于治疗组大鼠,每次冲击500次,间隔3天第2次治疗,第2次治疗结束后即刻对各组大鼠进行腓肠肌取材。采用HE染色观察肌纤维排列情况,免疫组化及Western blotting检测肌肉生长抑制素(Myostatin)、成肌分化抗原(Myod1)、肌细胞生成素(Myogenin)、胰岛素样生长因子-1(IGF-1)、磷脂酰肌醇-3激酶(PI3K)、蛋白激酶B(AKT)、磷酸化蛋白激酶B(p-AKTs473)的蛋白表达。结果:(1)HE染色可见:模型组较正常组肌细胞排列间隙增大,肌卫星细胞迁移至损伤处,出现少量单核或多核肌小管;治疗组细胞排列较规则,可见较多新生单核或多核肌管。(2)免疫组化结果显示:与正常组比较,模型组和治疗组Myostatin阳性表达均增多,治疗组阳性表达明显少于模型组(P<0.05),散在分布于细胞质之中。(3)Western blotting结果显示:与正常组相比,模型组Myod1的蛋白表达量增加,但不具有统计学意义(P>0.05),模型组和治疗组的Myogenin、PI3K、IGF-1、AKT、p-AKTs473均较正常组明显增加(P<0.05);与模型组相比,治疗组Myogenin蛋白表达量增加(P<0.05),Myod1、IGF-1、P-AKTs473蛋白表达量均增加(P<0.01),Myostatin蛋白表达量下降(P<0.05);PI3K和AKT蛋白表达量有所增加,但无统计学意义(P>0.05)。结论:冲击波治疗可促进骨骼肌钝挫伤修复,并且其正向调控作用与IGF-1/PI3K/AKT信号通路有关。 展开更多
关键词 骨骼肌钝挫伤 冲击波治疗 igf-1/pi3k/akt信号通路
下载PDF
上一页 1 2 3 下一页 到第
使用帮助 返回顶部