Growth inhibitory effect of triple anti-tumor gene transfer using Semliki Forest virus vector in glioblastoma cells.
The gene delivery of multiple tumor suppressors can provide an efficient tumor therapy in the case of malignant human glioblastomas containing multiple genetic alteration and inactivation. As such, the current study presents a new delivery system that can simultaneously express three anti-tumor genes using a Semliki Forest virus (SFV) vector in the expectation of combined or synergistic effects of angiogenesis inhibition by angiostatin and apoptosis induction by p53, PTEN and the rSFV particle itself. Recombinant SFV (rSFV) containing three anti-tumor genes (rSFV-Agt/p53/PTEN) were found to efficiently transduce and express each anti-tumor gene in glioblastoma cells. In addition, rSFV-Agt/p53/PTEN also resulted in a more effective induction of apoptosis in vitro and inhibition of tumor growth in nude mice when compared with other rSFVs containing only one or two anti-tumor genes. Accordingly, the current results demonstrate that a triple anti-tumor gene transfer using an rSFV vector would be a powerful strategy for regional cancer gene therapy.
Lee
Jong-Soo
JS
BioLeaders corporation, Daejeon, Korea.
Lee
Jun-Han
JH
Poo
Haryoung
H
Kim
Mi-Suk
MS
Lee
Seung-Hoon
SH
Sung
Moon-Hee
MH
Kim
Chul-Joong
CJ
D043168:Angiostatins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D005434:Flow Cytometry; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics*; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D008819:Mice, Nude; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012672:Semliki forest virus / Q000235:genetics; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D043168:Angiostatins; D051059:PTEN Phosphohydrolase