title: Downregulation of survivin by siRNA inhibits invasion and promotes apoptosis in neuroblastoma SH-SY5Y cells.
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.
authors.affiliation: Department of Pediatrics, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: H
authors.initials: H
authors.lastname: Liang
authors.affiliation: Department of Obstetrics, Qingdao Central Hospital, Qingdao, China.
authors.forename: W
authors.initials: W
authors.lastname: Cao
authors.affiliation: Department of Pediatrics, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: R
authors.initials: R
authors.lastname: Xu
authors.affiliation: Department of Pediatrics, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: X L
authors.initials: XL
authors.lastname: Ju
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051034:Inhibitor of Apoptosis Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000556:secondary*; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009447:Neuroblastoma / Q000473:pathology* / Q000556:secondary; D012334:RNA, Neoplasm / Q000187:drug effects / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D015853:Cysteine Proteinase Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D000077022:Survivin