Inhibition of lung cancer by transfer of p53 gene using Tie2-mediated gene delivery system
- Author:
Xiang-Hua WU
1
Author Information
1. Department of Medical Oncology
- Publication Type:Journal Article
- Keywords:
Gene therapy;
Genes p53;
Genetic vectors;
Lung neoplasms;
Receptor;
Tie-2
- From:
Tumor
2007;27(4):256-259
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To explore the therapeutic efficacy of transduction of p53 gene with Tie2-mediated gene delivery system in the treatment of lung cancer and provide experimental basis for future clinical application. Methods: GA3, a small peptide against Tie 2, was conjugated with PEI by bifunctional crosslinking agent SMCC to construct Tie2-targeted gene vector. Then pCMV-luciferase cDNA was combined with GA3-PEI to form an electrostatic complex. GA3-PEI/luciferase cDNA complex was transduced into Tie2-positive SPC-A1 lung cancer cells and Tie2-negative SMMC7721 hepatic cancer cells in vitro. The activity of luciferase was measured 24 h later. The GA3-PEI/β-gal complex was injected into peri-tumorous tissues of the transplanted SPC-A1 tumors in nude mice in vivo. Meanwhile, PEI/β-gal gene was injected as control. The nude mice were decapitated 24 h later. The heart, liver, spleen, lung, kidney and tumor tissues were excised and stained with X-gal. Human lung cancer SPC-A1 cells were inoculated subcutaneously into the 4-week-old female athymic mice (BALB/c). The mice were randomly divided into 5 groups (NS, GA3, p53, PEI/p53, and GA3-PEI/p53) with 6 mice in each group. GA3-PEI/ p53 1 μg was subcutaneously injected into peri-tumorous tissues once every two days. The tumor volume was calculated according to formula (V = πab2/6). The tumor-inhibiting ratio was calculated regarding NS group as control. Results: The activity of luciferase of GA3-PEI/luciferase was significantly higher in SPC-A1 cells than that in SMMC7721 cells (P<0.05). A lot of blue-stained cells were observed in transplanted tumor tissues but not in heart, liver, spleen, and kidney tissues except lung bronchial mucosa. Compared with NS group, GA3-PEI/p53 significantly inhibited the growth of tumor by 61.29%. Conclusion: Transfer of p.53 gene by GA3 gene delivery system remarkably inhibits tumor growth.
