Malignant neuroblastomas mostly occur in children and are frequently associated with N-Myc amplification. Oncogene amplification, which is selective increase in copy number of the oncogene, provides survival advantages in solid tumors including malignant neuroblastoma. We have decreased expression of N-Myc oncogene using short hairpin RNA (shRNA) plasmid to increase anti-tumor efficacy of the isoflavonoid apigenin (APG) in human malignant neuroblastoma SK-N-DZ and SK-N-BE2 cell lines that harbor N-Myc amplification. N-Myc knockdown induced morphological and biochemical features of neuronal differentiation. Combination of N-Myc knockdown and APG most effectively induced morphological and biochemical features of apoptotic death. This combination therapy also prevented cell migration and decreased N-Myc driven survival, angiogenic, and invasive factors. Collectively, N-Myc knockdown and APG treatment is a promising strategy for controlling the growth of human malignant neuroblastoma cell lines that harbor N-Myc amplification.
Keywords: 4′,6-diamidino-2-phenylindole; APG; Apigenin; Apoptosis; BSA; CTL; DAPI; Differentiation; FITC; GAPDH; HRP; ICAD; ID2; MMP-2; N-Myc shRNA; NF-κB; NFP; NSE; Neuroblastoma; PBS; PCNA; PI; PVDF; RT-PCR; SBDP; SDS-PAGE; VEGF; apigenin; b-FGF; basic fibroblast growth factor; bovine serum albumin; control; fluorescein isothocyanate; glyceraldehyde 3-phosphate dehydrogenase; hTERT; horseradish peroxidase; human telomerase reverse transcriptase; inhibitor of caspase-activated DNase; inhibitor of differentiation 2; matrix metalloproteinase-2; neurofilament protein; neuron specific enolase; nuclear factor-kappa B; phosphate-buffered saline; polyvinylidene fluoride; proliferating cell nuclear antigen; propidium iodide; reverse transcription-polymerase chain reaction; shRNA; short hairpin RNA; sodium dodecyl sulfate-polyacrylamide gel electrophoresis; spectrin breakdown product; vascular endothelial growth factor.
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