Angiostatin K(1-3) gene for treatment of human gliomas: an experimental study.
OBJECTIVE
To discuss the feasibility of gene therapy of human glioma by antiangiogenesis method.


METHODS
Angiostatin K(1-3) cDNA with secretive signal was inserted into the polylinker sites of eukaryotic expression vector pcDNA3 to construct pcDNA-SAK(1-3). The vector was transfected into human SHG44 glioma cells by lipofectamine and the positive clone was screened by G418. The biological characteristics of glioma cells were examined by electronmicroscope and flow cytometry. The activity of angiostatin K(1-3) protein expressed by SHG44 cells was examined by the bovine micrangium endotheliocyte inhibition assay and immunofluorescence assay. When SHG44 cells were implanted into the strata subcutaneum of nude mice, tumor necrosis and micrangium were calculated immunohistochemically and electronmicroscopically for determining their characteristics and validity in gene therapy of human glioma by antiangiogenesis method.


RESULTS
The eukaryotic expression vector pcDNA-SAK (1-3) was successfully constructed and transfected into glioma cells. The cells expressed angiostatin K(1-3) protein, and their tumorigenesis and angiogenesis in nude mice were greatly reduced.


CONCLUSIONS
Angiostatin K(1-3) gene is feasible to treat human glioma. This experiment lays a foundation for gene therapy of the other solid tumors by antiangiogenesis method.
Zhang
X
X
Institute of Neurosurgery of PLA, Xi Jing Hospital, Fourth Military Medical University, Xi'an 710032.
Wu
J
J
Fei
Z
Z
Gao
D
D
Li
X
X
Liu
X
X
Liang
J
J
Wang
X
X
D043168:Angiostatins; D000818:Animals; D001932:Brain Neoplasms / Q000628:therapy*; D005240:Feasibility Studies; D015316:Genetic Therapy; D005910:Glioma / Q000628:therapy*; D006801:Humans; D051379:Mice; D010446:Peptide Fragments / Q000235:genetics*; D010958:Plasminogen / Q000235:genetics*
D010446:Peptide Fragments; D043168:Angiostatins; D010958:Plasminogen