Highly efficient eradication of intracranial glioblastoma using Eg5 siRNA combined with HVJ envelope.
Gene Ther
; 16(12): 1465-76, 2009 Dec.
Article
in En
| MEDLINE
| ID: mdl-19675593
ABSTRACT
Hemagglutinating virus of Japan envelope (HVJ-E) vector with inactivated replication-defective Sendai virus was originally developed as a versatile drug delivery system. Recently, we have shown the direct tumor-killing activity of HVJ-E itself without therapeutic molecules in prostate cancer cells. Although human glioblastoma cells were also sensitive to HVJ-E treatment, complete eradication was not achieved using HVJ-E alone. Here, to develop more effective therapeutic strategy of glioblastoma, we enhanced the anti-tumor activity by incorporating Short interfering RNA (siRNA) of mitotic motor protein Eg5 into HVJ-E. Treatment with HVJ-E-containing Eg5 siRNA induced monopolar spindle formation and resulted in cell-cycle arrest and apoptosis. When HVJ-E-containing Eg5 siRNA was directly injected into an intradermal tumor xenograft, all mice became tumor-free. Similar results were observed in the intracranial tumor xenografts. The survival time of treated mice was significantly prolonged when HVJ-E was used. Histological examination showed that tumors remained in the brain after treatment with HVJ-E-containing negative control siRNA, but no tumors were detected after treatment with HVJ-E-containing Eg5 siRNA. This remarkable anti-tumor response was likely due to a synergistic effect of Eg5 siRNA and HVJ-E. Thus, this combination shows promise as an attractive novel therapy for glioblastoma.
Full text:
1
Collection:
01-internacional
Health context:
4_TD
/
6_ODS3_enfermedades_notrasmisibles
Database:
MEDLINE
Main subject:
Genetic Therapy
/
Viral Envelope Proteins
/
Kinesins
/
Glioblastoma
/
Sendai virus
/
RNA, Small Interfering
/
Oncolytic Virotherapy
Limits:
Animals
Language:
En
Journal:
Gene Ther
Year:
2009
Document type:
Article