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目的探讨CD151在骨肉瘤(OS)中的表达及其调控OS侵袭、转移的机理。方法培养、收集OS细胞和人成骨细胞后分离出质膜,通过液相色谱-质谱(LC-MS/MS)法比较质膜蛋白质组中CD151表达差异;通过免疫印记方法比较不同侵袭能力OS细胞系与成骨细胞中CD151表达差异;在OS组织与正常骨组织中,通过免疫组化方法比较CD151表达差异。应用siRNA抑制CD151表达,通过划痕实验研究OS迁移能力的变化。用String软件检测质膜蛋白质相互作用,分析CD151可能的作用机理。结果蛋白组学方法检测出342种质膜蛋白质,CD151在OS胞质膜中表达上调3.68倍,在高侵袭能力的OS细胞中表达上调更显著。抑制CD151表达后,OS细胞迁移能力下降。蛋白质相互作用结果显示,CD151通过β1-整合素与β-链蛋白发生关联。结论 CD151在OS中表达上调,可能通过经典Wnt通路影响OS侵袭、转移。 相似文献
103.
Retinal pigment epithelial (RPE) cells play critical roles in the maintenance of visual function, partly by secreting various biologically active factors that modulate the intraocular environment. Recent studies suggest involvement of Wnt proteins secreted by RPE cells in the pathogenesis of photoreceptor degeneration. In the present study, we examined, via the luciferase assay, the effect of media conditioned by RPE cells (RPE-CM) on activity of the canonical Wnt pathway in vitro. We isolated primary RPE cells from Long-Evans rats at P6-P9. In culture, these cells formed a monolayer with polygonal cell morphology and demonstrated repigmentation at confluency and immunoreactivity for ZO-1, a marker for tight junctions. To evaluate the effect of RPE-CM on the canonical Wnt pathway, we replaced the culture media of COS-7 cells transfected with (Tcf)(7)LUC, a multimeric Tcf-responsive element luciferase reporter construct, with RPE-CM and measured luciferase activity with or without Wnt3a or SB216763, a specific GSK3 inhibitor. RPE-CM did not enhance basal or Wnt3a-induced (Tcf)(7)LUC activity; instead, this activity decreased by 60%. RPE-CM also reduced SB216763-induced (Tcf)(7)LUC activity by 65%, which suggests that the inhibitory effect of RPE-CM is probably due to intracellular crosstalk rather than extracellular antagonism. RPE cells may thus be able to modulate the intraocular environment by regulating the canonical Wnt pathway. 相似文献
104.
Analysis of APC/beta-catenin genes mutations and Wnt signalling pathway in desmoid-type fibromatosis 总被引:2,自引:0,他引:2
OBJECTIVE: The abnormalities of the Wnt signalling pathway in desmoid-type fibromatosis were analysed, with the purpose of exploring the mechanism of tumorigenesis and progression. METHODS: The clinical and histopathological features of 96 cases were analysed. Beta-catenin, cyclin-D1, c-myc, and Ki-67 proteins were detected in 69 cases using formalin-fixed, paraffin-embedded tissues. Using the same materials, apoptosis of the tumour cells was investigated by terminal deoxynucleotidyl transferase mediated dUTP nick end-labelling (TUNEL) testing. Polymerase chain reaction (PCR), denaturing high performance liquid chromatography (DHPLC) assay, and sequencing were performed to detect abnormalities of the adenomatous polyposis coli (APC) and beta-catenin genes. RESULTS: APC gene mutations were found in 18 cases (26.1%, 18/69). Somatic mutations of codon 41 in exon 3 of beta-catenin were detected in 13 cases (18.8%, 13/69). No correlation of beta-catenin abnormal expression with the mutations of APC gene or beta-catenin gene was identified (p>0.05). The cases with abnormal beta-catenin expression showed a higher level of c-myc protein expression (69.7%, 23/33) than those without (22.2%, 8/36, p = 0.001). The apoptotic indices (AIs) were significantly lower in cyclin-D1 positive cases and c-myc positive cases (p = 0.015, p = 0.007). CONCLUSIONS: There are somatic mutations of the APC and beta-catenin gene in desmoid-type fibromatosis, and there are abnormalities in the Wnt signalling pathway. These abnormalities may result in aberrant cell proliferation and apoptosis, which are likely to be important factors in tumorigenesis and progression. 相似文献
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RhPDCD5 combined with dexamethasone increases antitumor activity in multiple myeloma partially via inhibiting the Wnt signalling pathway 下载免费PDF全文
Qian Cheng Liping Liu Yunfeng Fu Yanan Zhang Ye Yang Jing Liu 《Clinical and experimental pharmacology & physiology》2018,45(2):140-145
Multiple myeloma (MM) is one of the most common hematological malignancies and characterized by the clonal accumulation of malignant plasma cells. Significant progress has been made in MM treatment recently, while MM still remains incurable. Our previous studies showed that the recombined human programmed cell death 5 (rhPDCD5) can promote MM apoptosis induced by dexamethasone (Dex). Here, we expanded the findings by showing that the rhPDCD5 alone could not induce an obvious growth inhibition of U266 cells (a MM cell line). Of note, with the combination of dexamethasone (Dex), the growth of MM cells was significantly inhibited and accompanied with the cell cycle arrest in G0/G1. For mechanism study, we found that the combination treatment of rhPDCD5 plus Dex downregulated the mRNA and protein expressions of Wnt effectors including β‐catenin, β‐catenin (Ser675), TCF4, survivin and c‐Myc when compared to Dex only. Moreover, the activation of WNT pathway induced by LiCl can also be inhibited by this combination treatment. Taken together, our study demonstrated that the combination of rhPDCD5 and Dex can suppress the proliferation of multiple myeloma cells partially via inhibiting the WNT signalling pathway. 相似文献
107.
Haitao Sun Guanxin Chen Bin Wen Jialing Sun Haiyan An Jie Pang Wei Xu Xuemei Yang Songqi He 《Journal of pharmacological sciences》2018,136(3):133-141
Oligo-peptide I-C-F-6 is a Carapax trionycis extract component that has an effect on hepatic fibrosis, however, its mechanism of action is still unclear. This study investigated whether oligo-peptide I-C-F-6 could inhibit liver fibrosis by suppressing NF-κB and Wnt/β-catenin signaling, which are important in liver fibrosis. HSC-T6 cells were treated with oligo-peptide I-C-F-6, and rats were divided randomly into five groups: control (saline), CCl4, CCl4 plus oligo-peptide I-C-F-6 (0.12 and 0.24 mg/kg), and CCl4 plus colchicine (0.11 mg/kg). Here, we demonstrated that oligo-peptide I-C-F-6 ameliorated liver injury, inflammation, and hepatic fibrogenesis induced by CCl4. Oligo-peptide I-C-F-6 also inhibited the activation of hepatic stellate cells (HSCs) in vivo and in vitro, as evaluated by the expression of transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA), which is a specific marker of HSC activation. Moreover, oligo-peptide I-C-F-6 significantly reduced the expression and distribution of β-catenin, P-AKT, phospho (P)-GSK-3β, nuclear factor κB (NF-κB) P65, phospho-P65, and IκB kinase α/β (IKK-α/β) levels; additionally, IκB-α level was elevated both in vivo and in vitro. Together, these results indicate that oligo-peptide I-C-F-6 has hepatoprotective and anti-fibrotic effects in animal models of liver fibrosis, the mechanism of which may be related to modulating NF-κB and Wnt/β-catenin signaling. 相似文献
108.
109.
目的 探讨血清骨硬化蛋白(SOST)、Dickkopf-1(Dkk-1)蛋白与特发性股骨头坏死进展的相关性及临床意义。方法 纳入2017年1月~2020年6月于我院住院的特发性股骨头坏死患者76例作为观察组。同期选择76例性别、年龄(±1岁)、BMI(±1 kg/m2)与观察组配对的健康体检者作为对照组。检测两组血清SOST及Dkk-1蛋白水平并进行分析。结果 股骨头坏死患者血清SOST、Dkk-1蛋白水平显著高于对照组(P<0.05)。股骨头坏死患者血清Dkk 1蛋白表达与股骨头坏死ARCO分期呈正相关(r=0.341,P=0.003)。血清SOST与Dkk-1蛋白水平呈正相关(P<0.05)。ROC曲线分析示,血清SOST诊断股骨头坏死敏感性为51.30%,特异性为70.05%;血清Dkk-1诊断股骨头坏死敏感性为80.30%,特异性为63.90%(P<0.05)。结论 血清SOST、Dkk-1水平与病程进展密切相关,可作为预测股骨头坏死发生发展的重要指标及潜在的药物治疗靶点。 相似文献
110.
目的 探讨子痫前期(PE)患者胎盘组织中长链非编码RNA胃癌高表达转录本1(lncRNA GHET1)的表达及其对滋养层细胞增殖、细胞周期进展和侵袭能力的影响,并阐明其作用机制。 方法 30名孕产妇分为正常孕产妇组(正常组)15例和PE孕产妇组(PE组)15例,HE染色观察2组研究对象胎盘组织病理形态表现。体外培养滋养层HTR-8细胞,转染过表达lncRNA GHET1及对照序列质粒,并将滋养层细胞分为对照组(常规培养)、GHET1组(转染过表达lncRNA GHET1质粒)和阴性对照组(转染阴性对照序列质粒)。实时荧光定量PCR(RT-qPCR)法检测2组研究对象胎盘组织和各组HTR-8细胞中lncRNA GHET1 mRNA表达水平,CCK-8法检测各组HTR-8细胞增殖率,流式细胞术检测各组不同细胞周期HTR-8细胞百分率,Transwell小室实验检测各组HTR-8细胞侵袭能力,Western blotting法检测各组HTR-8细胞中细胞性骨髓细胞瘤病病毒癌基因(c-Myc)、细胞周期素D1(cyclinD1)、上皮细胞-间充质转化(EMT)相关蛋白E-钙黏蛋白(E-cadherin)和波形蛋白(Vimentin)蛋白表达 水平及Wnt/β-catenin信号通路中磷酸化糖原合成酶激酶3β(p-GSK3β)/糖原合成酶激酶3β(GSK3β)比值和β-连环蛋白(β-catenin)蛋白表达水平。 结果 与正常组比较,PE组患者胎盘组织绒毛发育不良,数量减少,绒毛内及间质血管分布紊乱,血管壁出现纤维素样坏死,钙化区域及绒毛上合体结节增加。与正常组比较,PE组患者胎盘组织中lncRNA GHET1 mRNA表达水平明显降低(P<0.05)。与对照组比较,GHET1组HTR-8细胞中lncRNA GHET1 mRNA表达水平明显升高(P<0.05),阴性对照组HTR-8细胞中lncRNA GHET1 mRNA表达水平差异无统计学意义(P>0.05)。与对照组比较,GHET1组HTR-8细胞增殖率、S期细胞百分率和侵袭细胞数明显升高(P<0.05),阴性对照组上述指标差异无统计学意义(P>0.05)。与对照组比较,GHET1组HTR-8细胞中c-Myc、cyclinD1、Vimentin和β-catenin蛋白表达水平及p-GSK3β/GSK3β比值均明显升高(P<0.05),E-cadherin蛋白表达水平明显降低(P<0.05),阴性对照组上述指标差异无统计学意义(P>0.05)。 结论 过表达lncRNA GHET1可能通过Wnt/β-catenin信号通路促进滋养层细胞增殖、细胞周期进展和细胞侵袭,发挥改善PE进展的作用。 相似文献