Glioma growth inhibition in vitro and in vivo by single chain variable fragments of the transferrin receptor conjugated to survivin small interfering RNA

Abstract

Inhibition of survivin by small interfering RNA (siRNA) can delay glioma growth. To enhance the effect of survivin-siRNA on intercranial glioma, a conjugate of siRNAsurvivin and single-chain variable fragment (scFv) of the transferrin receptor (TfR) was constructed and its effects assessed in vitro and in vivo. SurvivinsiRNA and the survivin-siRNA/scFv-TfR conjugate were constructed and used successfully to inhibit glioma U87 cell proliferation and enhance apoptosis in vitro. The molecular constructs were administered to an established U87 orthotopic mouse model. Western blot analysis and immunohistochemistry of the glioma tissues showed that survivin protein levels were strongly suppressed by the survivin-siRNA/scFv-TfR conjugate in vivo. Furthermore, survivin-siRNA/scFv- TfR prolonged the survival time of mice more than survivin-siRNA. In conclusion, the survivin-siRNA/scFv-TfR conjugate efficiently enhanced the effects of survivin-siRNA on glioma suppression in vivo, confirming the applicability of antibody-targeted molecular therapies for treating human brain tumours. © 2011 Field House Publishing LLP.