Anti-glioma effect of combination of bFGF-siRNA and Vpr in nude mice.
- Author:
Xue-quan FENG
1
;
Jin-huan WANG
;
Xin-nü XU
;
Biao ZHANG
;
Shu-jie WANG
;
Hong-sheng LIU
;
Na LIN
Author Information
- Publication Type:Journal Article
- MeSH: Adenoviridae; genetics; Animals; Apoptosis; Brain Neoplasms; metabolism; pathology; therapy; Cell Line, Tumor; Cell Proliferation; Fibroblast Growth Factor 2; genetics; metabolism; Gene Products, vpr; genetics; metabolism; Genetic Therapy; Glioma; metabolism; pathology; therapy; HIV-1; genetics; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; RNA, Small Interfering; genetics; Random Allocation; Recombinant Proteins; genetics; metabolism
- From: Chinese Journal of Oncology 2010;32(10):725-728
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo study the anti-glioma effect of recombinant adenovirus mediated combined gene therapy of bFGF-siRNA and HIV1-Vpr in vivo.
METHODSMouse glioma model was established by injecting 5 × 10(6) LN229 cells into BALB/c-nu nude mice. 30 nude mice were randomly divided into 5 groups: the negative control group, mock group, bFGF-siRNA group, Vpr group and combined therapy group, which at regular intervals were injected with PBS, rAd5-null, rAd5-bFGF-siRNA, rAd5-Vpr, rAd5-bFGF-siRNA plus rAd5-Vpr, respectively. The tumor volume was recorded every third day to draw a growth curve. After four weeks treatment, the mice were killed and specimens were taken. HE, immunohistochemical and TUNEL staining were performed to observe the cell morphology, detect the changes of relevant target proteins and cell apoptosis, respectively. Also the ultrastructural changes were observed by electron microscopy.
RESULTSThe tumor growth inhibition rates were 36.9%, 37.2% and 58.6% in the bFGF-siRNA group, Vpr group and combined therapy group, respectively, and the combined therapy group showed the most significant effect (P < 0.05). Also the results of HE, immunohistochemical and TUNEL staining revealed that the combined therapy group had the best effects on proliferation inhibition and apoptosis induced in glioma cells (P < 0.05). The most significant ultrastructural changes were observed in the combined therapy group.
CONCLUSIONThe combined gene therapy of bFGF-siRNA with Vpr shows a prominent and synergistic anti-glioma effect compared with that of mono-gene therapy in nude mice.
