[Gene transfer of von Hippel-Lindau inhibits the growth of transplanted solid tumors].
OBJECTIVE
To explore the effect of von Hippel-Lindau(VHL) gene on growth of EL-4 solid tumors in vivo.


METHODS
C57BL/6 mice model of solid tumors was established by subcutaneous injection of EL-4 lymphoma cells. Mice were randomly divided into two groups as treatment group (n=6) and control group (n=6) when tumor diameter increased to 0.1 cm and 0.4 cm respectively. Plasmid pcDNA3-VHL was injected into solid tumor in treatment group, empty pcDNA3 vector in control group. The growth of tumor was observed. Immunohistochemistry and Western blot analysis were used to examine the transgenic expression of VHL, hypoxia inducible factor-1alpha (HIF)-1alpha, bcl-2 and VEGF. Microvessel density (MVD) and apoptosis index (AI) of tumors were also detected.


RESULTS
VHL gene transfer eradicated tumors with small size (0.1 cm diameter), but it only retarded the growth of large tumors (0.4 cm diameter). VHL was overexpressed, the expression levels of VEGF, HIF-1alpha and bcl-2 were reduced in treatment group compared with those in the control group. The level of MVD was significantly lower in treatment group (P< 0.05), but AI was higher in treatment group compared with those in the control group (P< 0.01).


CONCLUSIONS
VHL gene therapy can inhibit the growth of EL-4 solid tumor in vivo.
Sun
Xue-ying
XY
Center of Hepatosplenic Surgery of Heilongjiang Province, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, China. kevsvn88@hotmail.com
Wang
Jian-li
JL
Tang
Bo
B
Liu
Feng-jun
FJ
Qiao
Hai-quan
HQ
Jiang
Hong-chi
HC
D000818:Animals; D005260:Female; D015316:Genetic Therapy; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000628:therapy*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000627:therapeutic use*
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C052617:Bcl2 protein, mouse; D051794:Von Hippel-Lindau Tumor Suppressor Protein