Antiangiogenic and antitumor effects of vascular endothelial growth factor small interfering RNA on Tca8113 human tongue squamous cell carcinoma xenografts in vivo.
- Author:
Da-hai YU
1
;
Jing LI
;
Ying CAO
;
Hai-bo CHEN
;
Jie HAO
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Apoptosis; Carcinoma, Squamous Cell; blood supply; genetics; pathology; Cell Line, Tumor; Humans; Mice; Mice, Nude; Neoplasm Transplantation; Neovascularization, Pathologic; prevention & control; RNA, Small Interfering; Tongue Neoplasms; blood supply; genetics; pathology; Vascular Endothelial Growth Factor A; genetics
- From: Chinese Journal of Stomatology 2008;43(9):556-560
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo examine the antiangiogenic and antitumor effects of vector-based small interfering RNA (siRNA) targeting vascular endothelial growth factor (VEGF) on human tongue squamous cell carcinoma xenografts in vivo.
METHODSTca8113 human tongue cancer nude mice xenograft model was established, and subsequently divided into four groups randomly (5/group). Two siRNA targeting VEGF constructed in eukaryotic expression vector (PU-VEGF-siRNA1, PU-VEGF-siRNA2) were injected intratumor and peritumor with lipofectamine 2000, respectively. No siRNA vector injected and non-injected tumors were used as experimented and negative controlled, respectively. Animals were injected one time every 3 days for a total of 10 times. Three days after the last injection, the weigh and volume of tumors, and intratumor microvessel density (MVD) were measured. The expression of VEGF in xenograft tumors was detected by reverse transcription polymerase chain reaction (RT-PCR), Western blotting and immunohistochemistry. The cell apoptosis and cell cycle analysis of tumors were detected by Tunel and Flow cytometry, respectively.
RESULTSCompared to the experimental and negative controls, the percentage of cells in the G(1) phase increased (P < 0.05), the expression of VEGF on both mRNA and protein level, the tumor weigh and volume, and MVD decreased in the PU-VEGF-siRNA2 group (P < 0.05), and more apoptosis was induced (P < 0.01). But significant differences were not noted between PU-VEGF-siRNA1 group and two controls (P > 0.05).
CONCLUSIONSVEGF-siRNA can reduce VEGF expression, inhibit tumor growth and angiogenesis, and induce apoptosis in Tca8113 cell carcinoma in vivo. Different VEGF-siRNA may have different effect in vivo.