Abstract
Neuroblastoma is a solid tumor that occurs mainly in children. Malignant neuroblastomas have a poor prognosis because conventional chemotherapeutic agents are not very effective. Survivin, a member of the inhibitor of the apoptosis protein family, plays a significant role in cell division, inhibition of apoptosis, and promotion of cell proliferation and invasion. Previous studies found that survivin is highly expressed in some malignant neuroblastomas and is correlated with poor prognosis. The aim of this study was to investigate whether survivin could serve as a potential therapeutic target of human neuroblastoma. We employed RNA interference to reduce survivin expression in the human neuroblastoma SH-SY5Y cell line and analyzed the effect of RNA interference on cell proliferation and invasion in vitro and in vivo. RNA interference of survivin led to a significant decrease in invasiveness and proliferation and increased apoptosis in SH-SY5Y cells in vitro. RNA interference of survivin inhibited tumor growth in vivo by 68±13% (P=0.002) and increased the number of apoptotic cells by 9.8±1.2% (P=0.001) compared with negative small interfering RNA (siRNA) treatment controls. Moreover, RNA interference of survivin inhibited the formation of lung metastases by 92% (P=0.002) and reduced microvascular density by 60% (P=0.0003). Survivin siRNA resulted in significant downregulation of survivin mRNA and protein expression both in vitro and in vivo compared with negative siRNA treatment controls. RNA interference of survivin was found to be a potent inhibitor of SH-SY5Y tumor growth and metastasis formation. These results support further clinical development of RNA interference of survivin as a treatment of neuroblastoma and other cancer types.
Highlights
Neuroblastoma is the predominant tumor of early childhood
We examined the expression of survivin in IMR32 and SH-SY5Y cell lines
We examined the downregulation of survivin mRNA and protein levels in neuroblastoma SH-SY5Y cells after stable survivin small interfering RNA (siRNA) or control siRNA transfection
Summary
Neuroblastoma is the predominant tumor of early childhood. It is the most common extracranial solid neoplasm in children, is responsible for 7% of malignancies in patients younger than 15 years of age, and represents ,15% of deaths from childhood cancer [1]. Based on the International Neuroblastoma Staging System, which considers stage, group, and tumor biology, patients are assigned to low-, intermediate-, or high-risk groups [2]. Despite advanced therapies including surgery, radiotherapy, and chemotherapy, children with high-risk neuroblastoma have an extremely poor prognosis [3]. The 5-year survival rate of high-risk patients is as low as 20-25%, and most patients develop metastatic dissemination [4].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
