Study of rAAV-TK-IRES-ES gene therapy of bladder cancer in vivo
10.3760/cma.j.issn.1000-6702.2009.04.018
- VernacularTitle:重组腺相关病毒-胸苷激酶-核糖体插入位点-内皮抑素双靶点基因治疗裸鼠膀胱癌的实验研究
- Author:
Jiangang PAN
;
Xing ZHOU
;
Ruifa HAN
- Publication Type:Journal Article
- Keywords:
Bladder neoplasms;
Adeno-associatcd virus;
Suicide gcne;
Endostatin
- From:
Chinese Journal of Urology
2009;30(4):262-264
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the therapeutically effect of rAAV-TIE model in vivo. Meth-ods Cell suspensions of T24 cells were injected into the subcutaneously of right scapular region of nude mice. The nude mice were raised under SPF condition and the xenograft tumor growth was ob-served. Bearing tumor nude mice were randomly divided into 5 groups: rAAV-MCS group, rAAV-Tk group, rAAV-ES group, rAAV-TIE group and control group. Four weeks later of treatment, the nude mice were sacrificed. The xenografts tumors were fixed for HE staining. The liver tissue and ne-phridial tissue were also fixed for HE stain. The blood sample and endostatin concentration was as-sayed by ELISA. Results After 3 weeks of injected with T24 cells on nude mice, 25 showed visible tumor on the injected location. The rate of tumor formation was 93%. After 9 days injected by rAAV-ES, rAAV-TK, rAAV-TIE, the tumor volume were: rAAV-ES group(0.75±0.08)cm3 , rAAV-TK group(0.71±0.11)cm3 , rAAV-TIE group(0.52±0.09)cm3 , rAAV-MCS group(1.27±0.13)cm3 and control group (1.24±0.17)cm3. The microvessel density in the different groups were as follow-ings: rAAV-ES group(18.72±2.53)/HP, rAAV-TK group(21.74±4.62)/HP, rAAV-TIE group (12.73±1.78)/HP, rAAV-MCS group(52.38±6.46)/HP and control group(49.94±7.17)/HP. The endostatin concentration in the diffcrent groups were as followings: rAAV ES group(38.52 6.53)μg/L and rAAV-TIE group(40.33±7.48)μg/L. HE staining confirmed the tumor. The liver tissue and kidncy tissue of each group had no obviously cell degeneration or necrosis. Conclusion The rAAV-TIE could inhibit tumor induced angiogenesis and suppress both the initiation and the subse-quent growth of human bladder cancer in nude mice model.