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). 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