Adenovirus-mediated double suicide gene therapy for experimental bladder carcinoma.
- Author:
Wan-long TAN
1
;
Yi XIE
;
Yuan-dong WU
;
Wen-hui ZHU
;
Shao-bin ZHENG
Author Information
- Publication Type:Journal Article
- MeSH: Adenoviridae; genetics; Animals; Cell Line; Cell Line, Tumor; Cytosine Deaminase; genetics; metabolism; Defective Viruses; genetics; Female; Flucytosine; pharmacology; therapeutic use; Ganciclovir; pharmacology; therapeutic use; Genes, Transgenic, Suicide; genetics; Genetic Therapy; methods; Genetic Vectors; Mice; Mice, Inbred C57BL; Neoplasm Transplantation; Thymidine Kinase; genetics; metabolism; Treatment Outcome; Urinary Bladder Neoplasms; pathology; therapy
- From: Journal of Southern Medical University 2006;26(5):594-597
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo evaluate the feasibility and efficacy of cytocine deaminase-thymidine kinase (CD-TK) fusion double suicide gene therapy using adenovirus mediated CD-TK gene and green fluorescent rotein (GFP) gene combined with ganciclovir(GCV) or 5-flourocytosine(5-FC) in a murine subcutaneous bladder carcinoma model.
METHODSA replication defective adenovirus vector containing CD-TK gene was used. Subcutaneous tumors were established in syngenic C57BL/6 female mice with 1 x 10(6) Mb49 cells. Intratumoral injection of AdCD-TK (1.58 x 10(8) PFU, qd x days) in combination with GCV (40 mg.kg(-1).d(-1), ip, qd x 10 days) or 5-FC (400 mg.kg(-1).d(-1), ip, qd x 10 days) was administered in vivo for the determination of treatment efficacy in separate controlled experiments.
RESULTSIn vivo experiments demonstrated that the mean volume of tumor in the group of AdCD-TK/GCV(326.58+/-109.56 mm(3)), AdCD-TK/5-FC (235.33+/-62.94 mm(3)) and AdCD-TK/(GCV+5-FC) (23.58+/-6.78 mm(3)) was reduced significantly compared with that of control group (993.51+/-158.32 mm(3)) (P=0.00), the mean volume of tumor in the group of AdCD-TK/(GCV+5-FC) was significantly less than that in the group of AdCD-TK/GCV or AdCD-TK/5-FC (P=0.04). Tumor necrosis was revealed by histomorphology compared with control animals.
CONCLUSIONSAdenovirus mediated CD-TK double suicide gene combining with GCV or 5-FC could provide an effective therapy in an experimental murine bladder carcinoma by significantly inhibiting tumor growth. The treatment efficacy of AdCD-TK combining GCV and 5-FC was superior to that of AdCD-TK combining GCV or AdCD-TK combining 5-FC.