Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

BACKGROUND Gastrointestinal stromal tumors(GISTs)are typical gastrointestinal tract neoplasms.Imatinib is the first-line therapy for GIST patients.Drug resistance limits the long-term effectiveness of imatinib.The regulatory effect of insulin-like growth factor 2(IGF2)has been confirmed in various cancers and is related to resistance to chemotherapy and a worse prognosis.AIM To further investigate the mechanism of IGF2 specific to GISTs.METHODS IGF2 was screened and analyzed using Gene Expression Omnibus(GEO:GSE225819)data.After IGF2 knockdown or overexpression by transfection,the phenotypes(proliferation,migration,invasion,apoptosis)of GIST cells were characterized by cell counting kit 8,Transwell,and flow cytometry assays.We used western blotting to evaluate pathway-associated and epithelial-mesenchymal transition(EMT)-associated proteins.We injected transfected cells into nude mice to establish a tumor xenograft model and observed the occurrence and metastasis of GIST.RESULTS Data from the GEO indicated that IGF2 expression is high in GISTs,associated with liver metastasis,and closely related to drug resistance.GIST cells with high expression of IGF2 had increased proliferation and migration,invasiveness and EMT.Knockdown of IGF2 significantly inhibited those activities.In addition,OEIGF2 promoted GIST metastasis in vivo in nude mice.IGF2 activated IGF1R signaling in GIST cells,and IGF2/IGF1R-mediated glycolysis was required for GIST with liver metastasis.GIST cells with IGF2 knockdown were sensitive to imatinib treatment when IGF2 overexpression significantly raised imatinib resistance.Moreover,2-deoxy-D-glucose(a glycolysis inhibitor)treatment reversed IGF2 overexpressionmediated imatinib resistance in GISTs.CONCLUSION IGF2 targeting of IGF1R signaling inhibited metastasis and decreased imatinib resistance by driving glycolysis in GISTs.

Exosome-transported IncRNA H19 regulates insulin-like growth factor-1 via the H19/let-7a/insulin-like growth factor-1 receptor axis in ischemic stroke

LncRNA(long non-coding RNA) H19 is a transcript of the H19 gene that is expressed during embryogenesis.We previously discove red a role for circular lncRNA H19 in the onset and prognosis of cerebral ischemic stroke.In this study,we used serum from patients with ischemic stroke,and mouse and cell culture models to elucidate the roles of plasma and neuronal exosomes in the regulatory effect of lncRNA H19 on insulin-like growth factor-1 and its mechanism in ischemic stroke,using western blotting,quantitative real-time polymerase chain reaction,and enzyme-linked immunosorbent assays.Plasma exosomal IncRNA H19 was negatively associated with blood levels of insulin-like growth factor-1 in samples from patients with cerebral ischemic stroke.In a mouse model,levels of exosomal IncRNA H19 were positively correlated with plasma and cerebral lncRNA H19.In a cell co-culture model,we confirmed that IncRNA H19 was transported from neuro ns to astrocytes by exosomes to induce downregulation of insulin-like growth factor-1 through the H19/let-7 a/insulin-like growth factor-1 receptor axis.This study provides the first evidence for the transpo rtation of IncRNA H19 by exosomes and the relationship between IncRNA H19 and insulinlike growth factor-1.

RNA interference affects tumorigenicity and expression of insulin-like growth factor-1,insulin-like growth factor-1 receptor,and basic fibroblast growth factor-2 in rat C6 glioma cells

BACKGROUND： Human gliomas are more likely to express basic fibroblast growth factor-2 （FGF-2） insulin-like growth factor-1（IGF-1）, and IGF-1 receptor （IGF-1R） than normal brain tissue. These factors activate signal transduction systems of Ras/MAPK and PI3K/Akl, which promote glioma growth. OBJECTIVE： To utilize RNA interference （RNAi） technique to down-regulate FGF-2, IGF-1, and IGF-1R gene expression, and to investigate the effects of these genes on rat C6 glioma cells, as well as the feasibility of RNAi for treating glioma. DESIGN, TIME AND SETTING： This neurooncological, randomized, controlled, in vivo and in vitro experiment, which used RNAi methodology, was performed at the Laboratory of Molecular Biology, Institute of Biochemistry, Chinese Academy of Sciences between August 2005 and February 2008. MATERIALS： Rat C6 cell lines were purchased from Shanghai Institute of Cellular Biology Affiliated to Chinese Academy of Sciences. Small interfering RNA （siRNA） was synthesized by Shanghai GenePharma. Anti-IGF-1, anti-IGF-1R, anti-FGF-2, anti-mouse and anti-rabbit IgG G1-HRP antibodies were provided by Santa Cruz Biotechnology, USA. Four to six week-old BALB/c nude mice were purchased from the Laboratory Animal Center, Chinese Academy of Sciences. METHODS： C6 glioma cells were transfected with siRNA, which was chemically synthesized in vitro to correspond to endogenous FGF-2, IGF-1, and IGF-1R genes. The inhibition ratio of targeting mRNA expression was detected by semiquantitative RT-PCR, and protein expression was determined by Western blot analysis. C6 glioma cell proliferation was observed using a growth curve C6 glioma cell apoptosis rate and cell cycle were detected by flow cytometry. C6 glioma cell growth regression was observed by transwell migration assay. In addition, nude mouse subcutaneous tumor models were used in this study. For studying the anti-tumor effects of IGF-1 and IGF-1R siRNA, two blank control groups, with six mice each, were set up： A （2.5 μg siRNA was injected one week after C6 cells were inoculated, Le., when tumor volume reached 8 mm × 8 mm） and B （siRNA was injected at the same time with C6 cells were inoculated. To study the effects of FGF-2 siRNA, the groups consisted of a blank control group, negative control group, 2.6 μg siRNA group, 4 μg siRNA group, and 5.3 μg siRNA group, with six mice each. MAIN OUTCOME MEASURES： mRNA and protein inhibition ratio of FGF-2, IGF-1, and IGF-1 R; C6 glioma cell proliferation, apoptosis, and cycle growth arrest; C6 glioma cell growth regression and subcutaneous tumorigenicity rates. RESULTS： All siRNA constructs proved to be effective. After 48 hours, transfection of 200 nmol/L siRNA resulted in a FGF-2 or IGF-1R gene inhibition ratio 〉 80% and an IGF-1 gene inhibition ratio of approximately 70%. Protein expression levels for FGF-2, IGF-1, and IGF-1R decreased in a dose-dependent manner following siRNA transfection, with an inhibition rate 〉 85%, 60%, and 50%, respectively. C6 glioma cell proliferation and apoptosis rates increased in proportion to siRNA. The apoptosis rate of C6 glioma cells induced by FGF-2, IGF-1, and IGF-1R siRNA was 39.96%, 15.07% and 22.47%, respectively （P 〈 0.01）. Transfection of 200 nmol/L IGF or IGF-1R siRNA for 48 hours suppressed C6 glioma cell migration. At 30 days after intratumoral injection of 2.6, 4, and 5.3 tJg FGF-2 siRNA, tumor growth regression rate of FGF-2 siRNA was 56%, 67%, and 86%, respectively. The tumor growth regression rate was 71.88% and 45.71%, respectively, when IGF-1 or IGF-1R siRNA was intratumorally injected 1 week after C6 glioma cell transplantation. When IGF-1 or IGF-1 R siRNA was intratumorally injected during C6 glioma cell transplantation, the tumor growth regression rate was 78.13% and 74.29%, respectively. CONCLUSION： siRNA transfection downregulated gene expression of FGF-2, IGF-1, and IGF-1R In addition, siRNA treatment markedly suppressed glioma cell proliferation, growth, and migration, and concomitantly reduced subcutaneous tumorigenicity.

Insulin-like growth factor-binding protein-3 inhibits IGF-1-induced proliferation of human hepatocellular carcinoma cells

OBJECTIVE Basic fibroblast growth factor(b FGF)and platelet-derived growth factor(PDGF)produced by hepatocellular carcinoma(HCC)cells are responsible for the cell growth.Accumulating evidence shows that insulin-like growth factor-binding protein-3(IGFBP-3)suppresses HCC cell proliferation in both IGF-dependent and independent manners.The present study is to investigate whether treatment with exogenous IGFBP-3 inhibits bF GF and PDGF production and the cell proliferation of HCC cells.METHODS Cell Counting Kit 8 assay were designed to detect HCC cell proliferation,transcription factor early growth response-1(EGR1)involving in IGFBP-3 regulation of b FGF and PDGF were detected by RT-PCR and Western blot assays.Western blot assay was adopted to detect the IGFBP-3 regulating insulin-like growth factor 1 receptor(IGF-1R)signaling pathway.RESULTS The present study demonstrates that IGFBP-3 suppressed IGF-1-induced b FGF and PDGF expression while it does not affect their expression in the absence of IGF-1.To delineate the underlying mechanism,Western-blot and RT-PCR assays confirmed that the transcription factor early growth response protein 1(EGR1)is involved in IGFBP-3 regulation of b FGF and PDGF.IGFBP-3 inhibition of type 1 insulin-like growth factor receptor(IGF1R),ERK and AKT activation is IGF-1-dependent.Furthermore,transient transfection with constitutively activated AKT or MEK partially blocks the IGFBP-3 inhibition of EGR1,b FGF and PDGF expression.CONCLUSION In conclusion,these findings suggest that IGFBP-3suppresses transcription of EGR1 and its target genes b FGF and PDGF through inhibiting IGF-1-dependent ERK and AKT activation.It demonstrates the importance of IGFBP-3 in the regulation of HCC cell proliferation,suggesting that IGFBP-3 could be a target for the treatment of HCC.

Effect of sericin on diabetic hippocampal growth hormone/insulin-like growth factor 1 axis

Previous studies have shown that sericin extracted from silk cocoon significantly reduces blood glucose levels and protects the nervous system against diabetes mellitus. In this study, a rat type 2 diabetes mellitus model was established by intraperitoneal injection of 25 mg/kg streptozotocin for 3 successive days, following which the rats were treated with sericin for 35 days. After treatment, the blood glucose levels of the diabetic rats decreased significantly, the growth hormone level in serum and its expression in the hippocampus decreased significantly, while the insulin-like growth factor-1 level in serum and insulin-like growth factor-1 and growth hormone receptor expression in the hippocampus increased significantly. The experimental findings indicate that sericin improves disorders of the growth hormone/insulin-like growth factor 1 axis to alleviate hippocampal damage in diabetic rats.

A predictive score for retinopathy of prematurity by using clinical risk factors and serum insulin-like growth factor-1 levels

AIM：To detect the impact of insulin-like growth factor-1（IGF-1）and other risk factors for the early prediction of retinopathy of prematurity（ROP）and to establish a scoring system for ROP prediction by using clinical criteria and serum IGF-1 levels.METHODS：The study was conducted with 127 preterm infants.IGF-1 levels in the 1st day of life,1st,2nd,3rd and4th week of life was analyzed.The score was established after logistic regression analysis,considering the impact of each variable on the occurrences of any stage ROP.A validation cohort containing 107 preterm infants was included in the study and the predictive ability of ROP score was calculated.RESULTS：Birth weights（BW）,gestational weeks（GW）and the prevalence of breast milk consumption were lower,respiratory distress syndrome（RDS）,bronchopulmonarydysplasia（BPD）and necrotizing enterocolitis（NEC）were more frequent,the duration of mechanical ventilation and oxygen supplementation was longer in patients with ROP（P〈0.05）.Initial serum IGF-1 levels tended to be lower in newborns who developed ROP.Logistic regression analysis revealed that low BW（〈1250 g）,presence of intraventricular hemorrhage（IVH）and formula feeding increased the risk of ROP.Afterwards,the scoring system was validated on 107 infants.The negative predictive values of a score less than 4 were 84.3%,74.7%and 79.8%while positive predictive values were 76.3%,65.5%and71.6%respectively.CONCLUSION：In addition to BW〈1250 g and IVH,formula consumption was detected as a risk factor for the development of ROP.Breastfeeding is important for prevention of ROP in preterm infants.

高血压合并焦虑病人血清微RNA-451a、胰岛素样生长因子-1受体表达水平与焦虑程度的关系

目的探讨高血压合并焦虑病人血清微RNA-451a(miR-451a)、胰岛素样生长因子-1受体(IGF1R)表达水平与焦虑程度的关系。方法选取2020年2月至2022年1月在汉中市中心医院进行治疗的高血压病人160例,根据临床诊断和汉密尔顿焦虑量表(HAMA)评估将病人分为高血压组60例、高血压合并轻度焦虑情绪组48例、高血压合并中度焦虑情绪组32例和高血压合并重度焦虑情绪组20例,收集整理所有病例的临床基础资料。采用实时荧光定量PCR法检测血清miR-451a表达水平、ELISA法检测血清IGF1R表达水平;比较分析高血压病人和高血压合并焦虑情绪病人的临床病理特征;采用Pearson法分析HAMA评分与血清miR-451a、IGF1R表达水平的相关性;采用logistic回归分析高血压合并焦虑的影响因素。结果高血压组、轻度焦虑、中度焦虑和重度焦虑组病人血清miR-451a水平依次降低(0.88±0.30,0.59±0.14,0.48±0.11,0.38±0.09),IGF1R水平依次升高[(2.14±0.60)μg/L,(2.66±0.62)μg/L,(3.08±0.66)μg/L,(3.51±0.74)μg/L];血清miR-451a水平与HAMA评分呈负相关(r=−0.50,P<0.05),血清IGF1R水平与HAMA评分呈正相关(r=0.43,P<0.05);高血压合并焦虑组收缩压[(142.26±18.51)mmHg,(135.29±17.84)mmHg]、舒张压[(84.25±11.30)mmHg,(78.23±10.25)mmHg]、C-反应蛋白[(4.47±0.96)mg/L,(4.16±0.91)mg/L]、IL-6水平[(36.95±6.31)μg/L,(27.48±5.49)μg/L]显著高于高血压组,IL-10水平[(12.34±3.26)ng/L,(16.24±3.91)ng/L]显著低于高血压组(P<0.05);多因素logistic回归分析结果显示,收缩压[OR 95%CI=1.33(1.06,1.67)]、舒张压[OR 95%CI=1.20(1.00,1.45)]、IL-6[OR 95%CI=1.89(1.22,2.93)]、IL-10[OR 95%CI=0.38(0.17,2.93)]、miR-451a[OR 95%CI=0.01(0.00,0.47)]、IGF1R[OR 95%CI=7.62(1.21,48.03)]水平为高血压合并焦虑的影响因素(P<0.05)。结论高血压合并焦虑病人血清中miR-451a低表达,IGF1R高表达,且与病人焦虑程度密切相关。

ACTR调控IGF-1R对肝癌细胞生长的影响

目的探究ACTR调控IGF-1R的表达对肝癌细胞生长的影响及意义。方法外源性免疫共沉淀、内源性免疫共沉淀检测ACTR与IGF-1R之间的相互作用。应用细胞免疫荧光共定位,检测ACTR与IGF-1R在肝癌细胞内共定位情况。qRT-PCR及Western blot实验,检测肝癌细胞中ACTR对IGF-1R表达的影响。将肝癌细胞系分为阴性对照组、转染ACTR组、敲低IGF-1R组、敲低IGF-1R+转染ACTR组,应用CCK8法测定各组细胞生长情况。结果外源性免疫共沉淀、内源性免疫共沉淀均证实ACTR与IGF-1R之间存在相互作用。细胞免疫荧光共定位证实ACTR与IGF-1R在肝癌细胞内存在共定位表达。qRT-PCR证实敲低ACTR后,IGF-1R mRNA表达水平降低(P<0.05),回转ACTR后IGF-1R mRNA表达水平亦可恢复。Western blot证实敲低ACTR后IGF-1R表达降低,而回转ACTR后IGF-1R表达可恢复。细胞生长曲线说明ACTR能够促进肝癌细胞的生长(P<0.05),当应用siRNA敲低IGF-1R后,ACTR的促细胞生长作用减弱。结论ACTR与IGF-1R之间存在相互的作用,IGF-1R介导了ACTR促进肝癌细胞生长的过程,ACTR/IGF-1R轴在肝癌细胞的生长中发挥了必要的作用,有可能成为治疗肝癌的靶点之一,为肝癌的防治提供新的思路。

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

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。

过表达miR-145-5p通过下调IGF1R抑制食管鳞状细胞TE-10细胞的恶性生物学行为

目的:探究miR-145-5p对食管鳞状细胞癌TE-10细胞增殖、侵袭、迁移和上皮间质转化(epithelial-mesenchymal transition,EMT)等恶性生物学行为的分子机制。方法:q PCR法检测miR-145-5p在食管鳞状细胞癌细胞和正常食管上皮细胞中的表达水平。采用双荧光素酶报告基因实验检测miR-145-5p与胰岛素样生长因子1受体(insulin-like growth factor 1 receptor,IGF1R)的靶向调控关系,Western blotting检测IGF1R蛋白和EMT相关蛋白的表达,CCK-8法和Transwell检测miR-145-5p/IGF1R分子轴对TE-10细胞增殖、侵袭、迁移的影响。结果:miR-145-5p在3株食管鳞状细胞癌细胞中低表达且在TE-10细胞中表达最低(P<0.01或P<0.05)。过表达miR-145-5p可显著抑制TE-10细胞的增殖、侵袭、迁移和EMT进程(P<0.01或P<0.05)。双荧光素酶报告基因证实miR-145-5p靶向下调IGF1R表达(P<0.01)。回复实验进一步证实,与单独过表达IGF1R相比,同时过表达miR-145-5p和IGF1R能显著缓解IGF1R对TE-10细胞的增殖、侵袭、迁移和EMT进程的促进作用(P<0.01或P<0.05)。结论:过表达miR-145-5p通过靶向下调IGF1R进而抑制了食管鳞状细胞癌TE-10细胞的增殖、侵袭、迁移和EMT进程。

二花脸和大白猪的脂肪组织中GH-R、IGF-1和IGF-ⅠR基因表达的发育性变化

分别于出生当天、3、2 0、30、4 5、90、12 0、180日龄随机屠宰二花脸公、母猪各 4头 (30日龄仅有公猪 ) ,于 2 0、30、90、12 0、180日龄随机屠宰大白猪公猪 4头 ,采集背部皮下脂肪组织。用RT PCR方法 ,以 18SrRNA作内标 ,定量分析脂肪组织中生长激素受体 (GH R)、胰岛素样生长因子 1(IGF 1)及胰岛素样生长因子Ⅰ型受体 (IGF ⅠR)基因表达的发育性变化 ,并进行品种和性别间比较。结果表明 :脂肪组织中GH RmRNA的表达有明显的发育性变化及品种差异 ,二花脸母猪GH RmRNA水平出生时较低 ,4 5日龄达到高峰 ,之后维持稳定 ;二花脸公猪GH RmRNA水平在出生时较高 ,至 4 5日龄达到最高值 ,之后显著下降 ,但总体上没有性别差异 ;大白猪公猪GH RmRNA水平极显著低于二花脸公猪 (P <0 0 1)。脂肪组织中IGF 1mRNA的表达有明显的发育性变化及性别和品种差异 ,二花脸母猪显著低于公猪 (P <0 0 5 ) ,大白猪公猪极显著低于二花脸公猪 (P <0 0 1) ;脂肪组织中IGF ⅠRmRNA的表达有明显的发育性变化 ,但在总体上没有明显的性别和品种差异。结果提示 :猪脂肪组织中GH R、IGF 1和IGF ⅠR的基因表达有特定的发育模式 ,IGF 1基因表达的品种差异可能正是两品种猪脂肪沉积规律不同的主要原因之一。

绵羊皮肤中GHR、IGF-1和IGF-1R基因表达的发育性变化及品种特点

采用相对定量反转录多聚酶链式反应（RT-PCR）方法，以18S rRNA作内标，研究了罗米丽（Romilly Hillys）×中国美利奴（新疆军垦型）杂交一代优质细毛羊和哈萨克粗毛羊皮肤中生长激素受体（GHR）、胰岛素样生长因子1（IGF-1）和胰岛素样生长因子1受体（IGF-1R）mRNA发育性变化并进行了品种间比较。分别于30、60、90、135、180和255日龄称重、采毛样，并于30、90、135和255日龄采皮样。结果表明：粗毛羊和细毛羊体重、羊毛生长的发育模式没有明显的差异，30-135日龄体重迅速增加，135～255日龄增重十分缓慢；30-135日龄羊毛日增长逐渐增加，135-180日龄羊毛生长十分缓慢，而180-255日龄又上升到较高水平。粗毛羊皮肤中GHRmRNA在30～90曰龄显著增加（P〈0．05），90日龄达到高峰，此后显著下降（P〈0．05）；细毛羊在135日龄时GHR mRNA极显著地升高（P〈0．01），此后又极显著地下降。粗毛羊皮肤中IGF-1、IGF-1R mRNA30—90日龄上升，90日龄之后极显著下降（P〈0．01）：细毛羊皮肤中IGF—1、IGF-1R mRNA出生时较高，然后逐渐下降。品种之间比较，细毛羊GHR mRNA出现高峰晚于粗毛羊，135日龄高峰时显著地高于粗毛羊；粗毛羊IGF—1、IGF-1RmRNA在90日龄出现高峰，并极显著或显著地高于细毛羊；粗毛羊90日龄前GHR、IGF-1和IGF-1RmRNA高于细毛羊，之后低于细毛羊。结果提示：绵羊皮肤中GHR，IGF-1和IGF-1R基因表达有特定的发育模式，并存在品种差异。

拔毛·剃毛对绵羊皮肤中GHR·IGF-1·IGF-1R·KAP3.2和KAP6-1基因表达的影响

选取36只新疆细毛羊随机分成6组进行拔毛、剃毛处理,于第0、3、6、9、12、50天采集皮肤样品,用反转录多聚酶链式反应(RT-PCR)方法,定量分析绵羊皮肤中生长激素受体(GHR)、胰岛素样生长因子1(IGF-1)和胰岛素样生长因子1型受体(IGF-1R)、角蛋白关联蛋白KAP3.2和KAP6-1mRNA的相对丰度。实验结果显示,与对照组相比,剃毛可显著提高IGF-1的表达量,但对GHR、IGF-1R、KAP3.2和KAP6-1的表达量均无明显的影响;而拔毛对皮肤中GHRI、GF-1I、GF-1R、KAP3.2和KAP6-1基因表达均无明显影响。

姜黄素对阿尔茨海默病小鼠海马InR和IGF1R表达的影响

目的观察姜黄素对阿尔茨海默病(Alzheimer's disease,AD)模型APP/PS1双转基因小鼠胰岛素受体(insulin receptor,InR)和胰岛素样生长因子1受体(insulin-like growth factor 1 receptor,IGF1R)表达的影响。方法将3月龄的APP/PS1双转基因小鼠随机分为模型组、阳性罗格列酮对照组(每日10 mg/kg)、姜黄素大(每日400 mg/kg)、中(每日200 mg/kg)、小剂量组(100 mg/kg),正常组为相同背景非转基因小鼠。灌胃3个月后,应用免疫组织化学和Western blot方法进行检测。结果 InR和IGF1R免疫组化染色,模型组小鼠大脑海马CA1区较正常对照组InR阳性细胞明显增加(P<0.01),姜黄素干预组有所恢复;而模型组小鼠大脑海马CA1区较正常对照组IGF1R阳性细胞明显减少(P<0.01),姜黄素干预组有所恢复。Western blot检测海马InR和IGF1R的蛋白表达结果与免疫组织化学检测结果一致。结论姜黄素可以使APP/PS1双转基因小鼠海马增加的InR和减少的IGF1R得以恢复,改善APP/PS1双转基因小鼠胰岛素信号转导。

清心开窍方对Aβ25-35诱导原代海马神经元损伤IGF-1R、IRS-1及Aβ mRNA表达的影响

目的：研究清心开窍方对Aβ25-35诱导原代海马神经元细胞损伤胰岛素样生长因子1受体（insulin—like growth factor 1 receptor，IGF-1R）、胰岛素受体底物蛋白1（insulin receptor substrate-1，IRS-1）及β-淀粉样蛋白（β—amyloid，Aβ）基因表达的影响，探讨清心开窍方对神经元细胞的保护作用及其机制。方法：制备sD乳鼠原代海马神经元细胞，分为6组：正常对照组、模型组、尼莫地平组（1×107mol.L-1）、清心开窍方低、中、高剂量组（6.25、12.5、25mg/mL）。支持培养至第7天，各治疗组分别给予相应药物预处理24h后，模型组及各治疗组加入老化处理的Aβ25-35。（终浓度为10 μmol.L-1）共同作用24h，建立AD细胞模型。正常对照组给予相等体积的培养液继续孵育24h。采用CCK一8法检测各组的细胞活力，RT—PCR法检测各组IGF-1R、IRS-1和Aβ mRNA的表达水平。结果：模型组与正常对照组比较细胞活性明显降低（P〈0.01），而清心开窍方能有效改善细胞活性；RT—PCR法结果显示模型组IGF-1R mRNA明显降低（P〈0.01），IRS-1和Aβ mRNA表达均明显增加（P〈0.01），而不同浓度的清心开窍方处理后均能提高IGF-1R mRNA的表达（P〈0.01或P〈0.05），减少IRS-1和Aβ mRNA表达（P〈0.01或P〈0.05）。结论：清心开窍方能减轻β一淀粉样蛋白对神经元细胞的毒性作用，提高细胞存活率，保护海马神经元细胞。

蛋用鹌鹑IGF-1R基因的多态性与体尺性状相关性分析

类胰岛素生长因子1型受体(IGF-1R)基因是类胰岛素生长因子(IGFs)在生物体内发挥作用的主要效应器,对机体生长发育进程中有重要影响。为探讨IGF-1R基因多态性与蛋用鹌鹑体尺性状的相关性,采用PCR产物直接测序方法对中国黄羽鹌鹑、北京白羽鹌鹑、朝鲜鹌鹑3种蛋用鹌鹑的IGF-1R基因进行多态性分析,并对IGF-1R基因的多态性与鹌鹑体尺性状进行相关性分析。结果表明,在3个蛋用鹌鹑群体中检测到IGF-1R基因A57G和A72T两个突变位点,A57G位点发生了A/G碱基突变,有AA、AG和GG三种基因型;A72T位点发生了A/T碱基突变,有AA、AT和TT三种基因型。中国黄羽鹌鹑的A57G位点对胫长、胸骨长和胫围有显著影响(P<0.05),A72T位点对体质量和胸骨长有显著影响(P<0.05),组合基因型AGAA对体质量有显著影响(P<0.05),组合基因型AAAA对胫长、胸骨长、胫围有明显影响(P<0.05)。北京白羽鹌鹑的A57G位点对体质量、胫长、体长、胫围有显著影响(P<0.05),A72T位点对胸骨长有显著影响(P<0.05),组合基因型AAAA对体质量和胸骨长有显著影响(P<0.05),组合基因型AAAT、GGAA、GGAT对胫长有显著影响(P<0.05),组合基因型GGAA对胸深有显著影响(P<0.05)。朝鲜鹌鹑的A57G位点对体质量有显著影响(P<0.05),A72T位点对胸骨长和胫围有显著影响(P<0.05),组合基因型AGAA对体质量有显著影响(P<0.05),组合基因型AGAT对胫长和胸宽有显著影响(P<0.05)。因此,IGF-1R基因可以作为候选基因应用于蛋用鹌鹑体尺性状的分子标记辅助选择。

EGFR及IGF1R在非小细胞肺癌(NSCLC)中表达及临床意义的研究

目的探究EGFR及IGF-1R在非小细胞肺癌(NSCLC)中表达及临床意义。方法 90例NSCLC患者均接受肺癌完全性切除术,NSCLC患者的病理标本,用免疫组织化学法染色检测EGFR、IGF-1R在NSCLC组织及癌旁正常组织中的表达,并分析其表达情况与肿瘤病理及临床生物学行为之间的关系。结果 EGFR及IGF-1R在NSCLC组织中的阳性表达率明显高于癌旁正常组织(P<0.001),EGFR阳性表达与年龄、组织学类型、分化程度、肿瘤大小、淋巴结转移及临床分期显著相关(P<0.05),IGF-1R阳性表达与肿瘤大小、临床分期及淋巴结转移显著相关(P<0.05),且Spearman相关性分析提示,EGFR和IGF-1R在NSCLC中表达呈正相关。结论 EGFR及IGF1R表达水平与NSCLC临川和预后关系密切,两者之间可能存在协同或交叉作用,有望为探索NSCLC临床预后因素提供新的理论依据。

鼻咽癌中IGF-1R、p-ERK、c-fos和Ki-67蛋白的表达及意义

目的研究胰岛素样生长因子1受体(IGF-1R)蛋白与细胞增殖相关信号分子p-ERK、c-fos、Ki-67蛋白在鼻咽癌及鼻咽黏膜上皮细胞中的表达及意义。方法 SP法检测30例鼻咽癌、25例鼻咽黏膜上皮细胞中IGF-1R、p-ERK、c-fos、Ki-67蛋白的表达。结果 IGF-1R、p-ERK、c-fos和Ki-67蛋白在鼻咽癌细胞中阳性表达率分别为93.33%(28/30)、93.33%(28/30)、83.33%(25/30)、86.67%(26/30),在鼻咽黏膜上皮细胞中阳性表达率分别为36.00%(9/25)、28.00%(7/25)、20.00%(5/25)、4.00%(1/25),2组间差异有显著统计学意义(P<0.01);鼻咽癌中IGF-1R与p-ERK、c-fos、Ki-67蛋白阳性表达呈正相关(P<0.05);p-ERK与c-fos、Ki-67蛋白阳性表达呈正相关(P<0.01);c-fos和Ki-67蛋白阳性表达呈正相关(P<0.01)。结论鼻咽癌中IGF-1R蛋白过表达参与调控细胞增殖。

FGFR1和IGF1R在肺鳞癌中的表达及其临床意义

目的探讨成纤维生长因子受体1(FGFR1)、胰岛素样生长因子受体1(IGF1R)在肺鳞癌组织中的表达及两者的临床意义。方法采用免疫组化法检测260例肺鳞癌术后患者的癌组织及40例癌旁正常组织中FGFR1、IGF1R的表达,分析两者表达与临床病理特征及预后的关系。采用Kaplan-Meier法进行生存分析,用Cox回归模型分析影响肺鳞癌预后的独立因素。结果 FGFR1、IGF1R在肺鳞癌组织中的阳性表达率分别为51.92%(135/260)、55.4%(144/260),均明显高于癌旁正常组织的32.5%(13/40)、30.0%(12/40),差异均有统计学意义(P<0.05)。FGFR1在肺鳞癌组织中的表达与吸烟、淋巴结转移有关,IGF1R表达仅与淋巴结转移有关(P<0.005)。FGFR1、IGF1R蛋白阳性表达者的中位OS分别为38.21个月、38.48个月,均低于阴性表达者的42.55个月、42.51个月(P>0.05)。Cox多因素分析显示,FGFR1、IGF1R表达及淋巴结转移为肺鳞癌患者术后的独立预后因子。结论 FGFR1、IGF1R均参与了肺鳞癌的发生、发展,并且二者均为肺鳞癌的不良预后指标,并有望成为分子靶向治疗的新靶点。

玉米须多糖对糖尿病肾病小鼠IGF-1R和Grb10表达的影响

目的:通过研究玉米须多糖对糖尿病肾病小鼠尿糖、尿蛋白及肾脏IGF-1R和Grb10蛋白表达的影响,探讨玉米须多糖对于糖尿病肾病保护作用的分子机制。方法:腹腔注射链脲菌素(streptozotocin, STZ)建立糖尿病肾病模型,血糖试纸检测小鼠血糖,酶联免疫法检测尿蛋白,western blot法对比正常组、正常组+玉米须多糖组、模型组、模型组+玉米须多糖组小鼠肾脏p-IGF-1R、t-IGF-1R、Grb10蛋白表达。结果:模型组血糖、尿蛋白与正常组相比均明显增高,玉米须多糖干预组与模型组相比血糖、尿蛋白明显降低,差异有统计学意义(P<0.05);p-IGF-1R在模型组表达明显低于正常组,在模型组+玉米须多糖组中表达明显高于模型组,差异有统计学意义(P<0.05)。Grb10在模型组表达明显高于正常组,在模型组+玉米须多糖组中表达明显低于模型组,差异有统计学意义(P<0.05)。结论:玉米须多糖可能通过影响IGF-1R信号通路中IGF-1R的活性和Grb10蛋白的表达,达到改善糖尿病肾病肾脏功能、保护肾脏的作用。