Targeting gene therapy for bladder cancer using human UroplakinⅡ promoter / 中华泌尿外科杂志

ABSTRACT

Objective To investigate the feasibility of tissue-specific gene therapy for bladder cancer using human UroplakinⅡ(UPⅡ) promoter. Methods The recombinant adenoviruses,Ad-hUPⅡ-TNF carrying tumor necrosis factor (TNF-?) under control of the hUPⅡ,were generated.ELISA showed the production and secretion of TNF by bladder cancer cells infected with Ad-hUPⅡ-TNF.The level of TNF in urine was identified with ELISA. Results ELISA showed that production and secretion of TNF by bladder cancer cells infected with Ad-hUPⅡ-TNF was distinctly higher than by non-urothelium cells infected with Ad-hUPⅡ-TNF and MTT showed that proliferation of bladder cancer cells was obviously inhibited.Conditioned medium from bladder cancer cells apparently inhibited cells of L929 proliferation,compared with conditioned medium from non-bladder cells by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.Intravesical inoculation of Ad-hUPⅡ-TNF also caused decreased tumor growth in orthotopic human bladder cancer model.The sustained high level of TNF in urine could be identified with ELISA. Conclusions TNF driven by hUPⅡ promoter has effective active in the inhibition of bladder cancer growth both in vivo and in vitro.These will undoubtedly yield a new approach of therapy for bladder cancer.