Gene transfer of von Hippel-Lindau inhibits the growth of transplanted solid tumors.
- Author:
Xue-ying SUN
1
;
Jian-li WANG
;
Bo TANG
;
Feng-jun LIU
;
Hai-quan QIAO
;
Hong-chi JIANG
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Female; Genetic Therapy; Hypoxia-Inducible Factor 1, alpha Subunit; metabolism; Mice; Mice, Inbred C57BL; Neoplasms, Experimental; blood supply; therapy; Neovascularization, Pathologic; therapy; Proto-Oncogene Proteins; metabolism; Proto-Oncogene Proteins c-bcl-2; Transfection; Vascular Endothelial Growth Factor A; metabolism; Von Hippel-Lindau Tumor Suppressor Protein; therapeutic use
- From: Chinese Journal of Gastrointestinal Surgery 2005;8(3):241-244
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo explore the effect of von Hippel-Lindau(VHL) gene on growth of EL-4 solid tumors in vivo.
METHODSC57BL/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.
RESULTSVHL 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).
CONCLUSIONVHL gene therapy can inhibit the growth of EL-4 solid tumor in vivo.
