Targeting survivin suppresses proliferation and invasion of retinoblastoma cells in vitro and in vivo

Survivin is a member of the inhibitor of apoptosis (IAP) family and has multifunctional properties that include aspects of proliferation, invasion and cell survival control. Survivin is a promising candidate for targeted cancer therapy as its expression is associated with poor clinical outcome and more aggressive clinicopathologic features. Retinoblastoma (RB) is a highly invasive malignant tumor that often invades the brain and metastasizes to distal organs through the blood stream. However, expression of survivin in RB has not been previously characterized. In addition, whether survivin could be used for targeted RB therapy is not clear. In the present study, we demonstrated that RB tumors with invasion showed significantly higher expression of survivin compared to tumors without invasion (P < 0.05). High-risk tumors showed significantly increased expression of survivin compared to tumors with low risk (P < 0.05). Survivin inhibition by targeted siRNA suppresses the proliferation, growth, invasion, imgration and induced apoptosis of retinoblastoma Y79 cells in vitro. In addition, Survivin inhibition by targeted shRNA suppresses in vivo orthotopic tumors and liver metastasis in BALB/c nude mice. In line with these results, surviving siRNA (shRNA) effectively induces down-regulation of target genes of surviving by western blot, RT-PCR and immunohistochemistry analysis. In conclusion, high survivin expression is associated with invasion and metastasis in RB. We suggest that survivin inhibition could be a potential therapeutic approach in retinoblastoma through suppressing tumor proliferation and invasion.