The Effects of combined therapy of Phosphatidylinositol 3p-Kinase inhibitor and Ad-PTEN in human glioma nude mice model
- VernacularTitle:PI3K抑制剂联合Ad-PTEN对裸鼠移植胶质瘤的治疗作用
- Author:
Yunpeng SONG
;
Zhe LIU
;
Yue ZHONG
;
Chunsheng KANG
;
Peng XU
;
Lei HAN
;
Anling ZHANG
;
Guangxiu WANG
;
Zhifan JIA
;
Peiyu PU
- Publication Type:Journal Article
- Keywords:
Glioma;
Phosphatidylinositol 3-Kinase inhibitor;
PTEN
- From:
Chinese Journal of Nervous and Mental Diseases
2010;36(2):104-107
- CountryChina
- Language:Chinese
-
Abstract:
Objective Increasing evidence suggest that aberrant activation of PI3K/Akt is involved in many human cancers, and that inhibition of the PI3K/Akt pathway might be a promising strategy for cancer therapy. The study is to evaluate the effects of combined therapy of PI3K inhibitor (LY294002) and Ad-PTEN in athymic mice xenogeneic transplant model of human glioma and to reveal the possible mechanisms involved.Methods Twenty-four athymic mice were randomly divided into 4 groups (DMSO、Ad-vector plus DMSO、LY294002 alone and Ad-PTEN plus LY294002), and were treated, respectively. Athymic mice xenogeneic transplant model was established by inoculation (sc) with LN229 glioma cells. Body mass (BM) and diameter of tumor mass were measured. Furthermore, The protein expressions of PTEN、p-Akt、CyclinD1、Caspase-3、MMP-2、p-FAK in tumor tissues were analyzed with immunohistochemistry.Results The tumor-inhibiting rate of was significantly higher in Ad-PTEN plus LY294002 than in the LY294002 alone (92.46 vs 65.59%)( P <0.05).The protein expressions of PTEN and Caspase-3 were significantly higher, while PCNA、CyclinD1、bcl-2 and MMP-2、p-FAK was significantly lower in Ad-PTEN plus LY294002 group than in the other three groups ( P <0.05).Conclusions LY294002 plus Ad-PTEN achieve better outcome than either alone in treating glioma possibly through enhancement of the inhibitory action of PI3K/Akt pathway and Ad-PTEN pathway.