Β‐CATENIN

β - CATENIN
  • 文章类型: Journal Article
    尽管上皮-间质标志物在前列腺癌(PC)中起重要作用,需要进一步的研究来更好地了解它们在诊断中的效用,癌症进展预防,和治疗抗性预测。我们的研究包括111例经尿道电切术的PC患者,以及16个健康对照。逆转录-定量聚合酶链反应(RT-qPCR)用于检测E-cadherin的表达,β-连环蛋白,还有Vimentin.我们发现E-cadherin和β-catenin在原发性PC组织中表达不足。发现E-cadherin表达与前列腺特异性抗原进展呈负相关(PSA-P;进展的血清标志物;p=0.01;|r|=0.262)。此外,两个标记的减压,E-钙粘蛋白和β-连环蛋白,发现与晚期肿瘤分期和分级相关(p<0.05)。另一方面,波形蛋白在PC患者中过度表达,倍数变化为2.141,与诊断相关,预后,以及对雄激素剥夺疗法的治疗抗性的预测(p=0.002),阿比特龙-酸(p=0.001),和紫杉烷(p=0.029)。此外,目前的研究强调,在初次手术后进展的患者中,生存率明显下降,没有使用药物,并异常表达了这些基因。在Cox回归多变量分析中(p<0.05),在PC患者中,Vimentin标志物与冠心病呈正相关(p=0.034).总之,本研究强调了诊断性(p<0.001),预后(p<0.001),波形蛋白在原发性PC中的治疗潜力(p<0.05),以及它对心血管疾病的影响。此外,我们证实了E-cadherin和β-catenin的潜在预后价值。
    Although epithelial-mesenchymal markers play an important role in prostate cancer (PC), further research is needed to better understand their utility in diagnosis, cancer progression prevention, and treatment resistance prediction. Our study included 111 PC patients who underwent transurethral resection, as well as 16 healthy controls. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to examine the expression of E-cadherin, β-catenin, and Vimentin. We found that E-cadherin and β-catenin were underexpressed in primary PC tissues. E-cadherin expression was found to be inversely associated with prostate-specific antigen progression (PSA-P; serum marker of progression; p = 0.01; |r| = 0.262). Furthermore, the underexpression of two markers, E-cadherin and β-catenin, was found to be associated with advanced tumor stage and grade (p < 0.05). On the other hand, Vimentin was overexpressed in PC patients with a fold change of 2.141, and it was associated with the diagnosis, prognosis, and prediction of treatment resistance to androgen deprivation therapy (p = 0.002), abiraterone-acid (p = 0.001), and taxanes (p = 0.029). Moreover, the current study highlighted that poor survival could be significantly found in patients who progressed after primary surgery, did not use drugs, and expressed these genes aberrantly. In Cox regression multivariate analysis (p < 0.05), a positive correlation between the Vimentin marker and coronary heart disease in PC patients was identified (p = 0.034). In summary, the present study highlights the diagnostic (p < 0.001), prognostic (p < 0.001), and therapeutic potential of Vimentin in primary PC (p < 0.05), as well as its implications for cardiovascular disease. Furthermore, we confirm the potential prognostic value of E-cadherin and β-catenin.
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  • 文章类型: Journal Article
    Wnt/β-catenin信号通路在肿瘤的发生发展中发挥着重要作用,器官发生,和胚胎发生。异常激活促进癌症干细胞的更新,扩散,和差异化。在本研究中,分子对接模拟和ADMET研究进行了选择的生物活性化合物,以寻找β-catenin蛋白抑制剂,用于发现抗癌药物。在AutodockVina上使用PyRx软件进行盲对接仿真。β-连环蛋白蛋白(PDBID:1jdh)和313种生物活性化合物(来自PubChem数据库)与选定的标准抗癌药物用于分子对接。使用SwissADME和pkCMS网络服务器计算性能最佳的化合物的ADMET特性。分子对接研究结果表明,甘草酸,茄碱,PolyphylinI,crocin,金丝桃素,土贝莫苷-1,地奥司明,根据它们的结合亲和力,芦丁与β-catenin蛋白具有最佳的结合相互作用。甘草酸和茄碱具有相同且最低的结合能-8.5kcal/mol。其次是-8.4kcal/mol的多叶黄素I,和Crocin,金丝桃素,和tubeimoside-1,它们的结合能均为8.1kcal/mol。其他表现最好的化合物包括具有-8.0kcal/mol的结合能的地奥司明和芦丁。ADMET研究表明,以下化合物甘草酸,茄碱,PolyphylinI,crocin,金丝桃素,土贝莫苷-1,地奥司明,芦丁,和黄芩苷都违反了Lipinski的5法则,这意味着口服生物利用度差。然而,根据结合能得分,有人认为,这些药理活性化合物是潜在的抗癌分子。
    Wnt/β-catenin signaling pathway plays a role in cancer development, organogenesis, and embryogenesis. The abnormal activation promotes cancer stem cell renewal, proliferation, and differentiation. In the present study, molecular docking simulation and ADMET studies were carried out on selected bioactive compounds in search of β-catenin protein inhibitors for drug discovery against cancer. Blind docking simulation was performed using PyRx software on Autodock Vina. β-catenin protein (PDB ID: 1jdh) and 313 bioactive compounds (from PubChem database) with selected standard anticancer drugs were used for molecular docking. The ADMET properties of the best-performing compounds were calculated using SwissADME and pkCMS web servers. The results obtained from the molecular docking study showed that glycyrrhizic acid, solanine, polyphyllin I, crocin, hypericin, tubeimoside-1, diosmin, and rutin had the best binding interactions with β-catenin protein based on their binding affinities. Glycyrrhizic acid and solanine had the same and lowest binding energy of -8.5 kcal/mol. This was followed by polyphyllin I with -8.4 kcal/mol, and crocin, hypericin, and tubeimoside-1 which all had a binding energy of 8.1 kcal/mol. Other top-performing compounds include diosmin and rutin with binding energy of -8.0 kcal/mol. The ADMET study revealed that the following compounds glycyrrhizic acid, solanine, polyphyllin I, crocin, hypericin, tubeimoside-1, diosmin, rutin, and baicalin all violated Lipinski\'s rule of 5 which implies poor oral bioavailability. However, based on the binding energy score, it was suggested that these pharmacologically active compounds are potential molecules to be tested against cancer.
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