Discovery of Dual targeting PEGylated BG-P1600-TAT to Norepinephrin Transporter (NET) and Thyrointegrin αvβ3 in the Treatment of Neuroblastoma cancer cellline. Discovery of Dual targeting PEGylated BG-P1600-TAT to Norepinephrin Transporter (NET) and Thyrointegrin αvβ3 in the Treatment of Neuroblastoma cancer cellline

Molecular mechanisms of anti-cancer activities of BG-P1600-TAT were explored employing genome-wide expression profiling experiments. Human neuroblastoma cell line SK-N-FI and primary cells SKNAS were treated with 30µM of the BG-P1600-TAT for 48 hours, harvested, and total RNA was immediately isolated from three biological replicates of control (vehicle-treated) and BG-P1600-TAT-treated cells. Gene expression profiling experiments identified 14-gene BG-P1600-TAT molecular interference signature captured most biologically important significantly enriched records reflecting the putative molecular mechanisms of anti-cancer activities of the BG-P1600-TAT. In BG-P1600-TAT treated SK-N-FI cells, 753 differentially expressed genes (DEGs) were identified compared to control vehicle-treated cells. Among 753 DEGs, 427 genes were down-regulated and 326 genes were up-regulated. In SKNAS cells, BG-P1600-TAT showed a significant effects on signal transduction pathways activated during cellular responses to IL-1alpha, TNF-alpha, EGF, TGF, PDGF, and AR. Further BG-P1600-TAT also showed a significant effect on multiprotein complexes of potential biological and therapeutic significance, including several complexes engaged during apoptosis (BCL-2 family protein complex; Survivin complex; BAX complex; Caspase complex), angiogenesis (VEGF-A complex; Thrombospondin complex), and cell adhesion (Galectin complex; Integrin alpha/beta complexes). Overall design: Genome-wide expression profiling experiments were carried out to gain insights into biological and molecular functions of genes expression of which was significantly affected in neuroblastoma cells by the BG-P1600-TAT treatment. RNA isolation from three biological replicates of control SK-N-FI cells compared with SK-N-FI cells treated with BG-P1600-TAT (30 µM) for 48 h. Further neuroblastoma primary cells SKNAS (control) compared with SKNAS cells treated with BG-P1600-TAT (30 µM) for 48 h

本数据集通过全基因组表达谱实验，探究了BG-P1600-TAT的抗癌活性分子机制。将人神经母细胞瘤细胞系SK-N-FI及原代细胞SKNAS以30μM浓度的BG-P1600-TAT处理48小时后收集细胞，分别从对照组（溶剂处理组）与BG-P1600-TAT处理组的3次生物学重复样本中提取总RNA。基因表达谱分析鉴定得到14基因BG-P1600-TAT分子干扰特征，该特征可有效捕捉反映BG-P1600-TAT抗癌活性潜在分子机制的、具有重要生物学意义的显著富集条目。与溶剂处理的对照组相比，经BG-P1600-TAT处理的SK-N-FI细胞中共鉴定出753个差异表达基因（differentially expressed genes, DEGs），其中427个基因表达下调，326个基因表达上调。在SKNAS细胞中，BG-P1600-TAT可显著影响细胞响应IL-1α、TNF-α、EGF、TGF、PDGF及AR时激活的信号转导通路。此外，BG-P1600-TAT对具有潜在生物学与治疗价值的多蛋白复合物亦存在显著调控作用，包括参与细胞凋亡的多种复合物（BCL-2家族蛋白复合物、Survivin复合物、BAX复合物、Caspase复合物）、血管生成相关复合物（VEGF-A复合物、血小板反应蛋白复合物）以及细胞黏附相关复合物（半乳糖凝集素复合物、整合素α/β复合物）。实验整体设计：本研究通过全基因组表达谱实验，旨在解析神经母细胞瘤细胞中受BG-P1600-TAT处理显著影响的基因的生物学与分子功能。具体分为两组对照：① 3次生物学重复的对照组SK-N-FI细胞，与经30μM BG-P1600-TAT处理48小时的SK-N-FI细胞；② 原代神经母细胞瘤细胞SKNAS对照组，与经30μM BG-P1600-TAT处理48小时的SKNAS细胞。