Sequential hTERT Knockdown and Apigenin Treatment Inhibited Invasion and Proliferation and Induced Apoptosis in Human Malignant Neuroblastoma SK-N-DZ and SK-N-BE2 Cells

被引:0
作者
Mrinmay Chakrabarti
Naren L. Banik
Swapan K. Ray
机构
[1] University of South Carolina School of Medicine,Department of Pathology, Microbiology, and Immunology
[2] Medical University of South Carolina,Department of Neurosciences
来源
Journal of Molecular Neuroscience | 2013年 / 51卷
关键词
Apigenin; Apoptosis; hTERT; Invasion; Neuroblastoma; shRNA;
D O I
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学科分类号
摘要
Human telomerase reverse transcriptase (hTERT) plays a key role in conferring immortality to human malignant neuroblastomas. We first determined differential expression of hTERT in four human malignant neuroblastoma SH-SY5Y, SK-N-DZ, SK-N-BE2, and IMR-32 cell lines. We then used SK-N-DZ and SK-N-BE2 cell lines, which showed the highest expression of hTERT, to investigate the therapeutic effects of sequential hTERT knockdown and apigenin (APG) treatment. We performed cell invasion assay and studied alterations in expression of matrix metalloproteinases and cell cycle regulatory molecules after this combination therapy. We also investigated induction of apoptosis by using in situ Wright staining, Annexin V staining, and Western blotting. Sequential hTERT knockdown and APG treatment significantly downregulated expression of hTERT so as to cause over 90 % inhibition of cell invasion and 70 % induction of apoptosis in both SK-N-DZ and SK-N-BE2 cell lines. Western blotting demonstrated downregulation of the molecules involved in cell invasion and proliferation, but upregulation of the cell cycle inhibitor and apoptosis-inducing molecules. In conclusion, our current results clearly showed that sequential hTERT knockdown and APG treatment could be a promising therapeutic strategy for effective inhibition of invasion and proliferation and induction of apoptosis in hTERT overexpressing malignant neuroblastoma cells.
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页码:187 / 198
页数:11
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