title: 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 siRNA-survivin 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.
authors: Department of Neurosurgery, Affiliated Hospital of Inner Mongolia Medical College, Hohhot, China.
authors: F
authors: F
authors: Wang
authors: H-R
authors: HR
authors: Bai
authors: J
authors: J
authors: Wang
authors: Y-Z
authors: YZ
authors: Bai
authors: C-W
authors: CW
authors: Dou
mesh_terms: D000818:Animals; D017209:Apoptosis; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D051379:Mice; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D034741:RNA, Small Interfering / Q000494:pharmacology* / Q000627:therapeutic use; D011990:Receptors, Transferrin / Q000378:metabolism*; D057127:Single-Chain Antibodies / Q000494:pharmacology* / Q000627:therapeutic use; D000077022:Survivin; D023041:Xenograft Model Antitumor Assays
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D034741:RNA, Small Interfering; D011990:Receptors, Transferrin; D057127:Single-Chain Antibodies; D000077022:Survivin