[An experimental research on the combination treatment of sFLK-1 gene therapy combined with gamma knife].
OBJECTIVE
To evaluate whether the sustained expression by adenovirus-mediated gene (sFLK-1) transfer can enhance the treatment efficacy of gamma knife radiosurgery.


METHODS
The mouse sFLK-1 gene was cloned to construct the recombinant adenovirus. The gliomata growing in BALB/c female nude mice with an initial mean volume of (109.3 +/- 20.5) mm3 were treated with gamma knife alone (13 Gy on day 12), sFLK-1 adenovirus alone (1 x 10(9) plaque-forming units, PFU was given to two mouse tail vein by injections, 7 and 14 days), gamma knife associated with sFLK-1 adenovirus or control adenovirus (1 x 10(9) PFU was given to two mouse tail vein by injections, 13 and 17 days). After the completion of therapy, the tumor size was recorded. The microvessel density (MVD) and tumor apoptosis were evaluated by immunohistochemical means.


RESULTS
As comparing with three other control groups, the combination treatment group with sFLK-1 gene therapy and gamma knife not only significantly reduced tumor volume and prolonged the life span of tumor burden mice as well. In addition, the average tumor weights were lower in sFLK-1 combined with gamma knife group than in any other control group. Immunohistochemical analysis of glioma demonstrated a decreased MVD and a high apoptosis cell rate in sFLK-1 combined with gamma knif group.


CONCLUSIONS
The antitumor effect of gamma knife can be potentiated by sFLK-1 gene therapy. Thus the combination of sFLK-1 gene therapy and gamma knife results an additive effect of antitumor. The observation may provide an important strategy for treatment cancer metastasis.
Chen
Jing
J
Biomedical Engineering, West China of Preclinical and Forensic Medicine, Sichuan University, Chengdu, 610041, China.
Wang
Zheng-rong
ZR
Li
Hao
H
Wei
Yu-quan
YQ
Wang
Wei
W
Zhu
Bin
B
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001932:Brain Neoplasms / Q000601:surgery / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D005910:Glioma / Q000601:surgery / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016634:Radiosurgery; D051381:Rats; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis / Q000235:genetics*
D040301:Vascular Endothelial Growth Factor Receptor-2