p53 protein transduction therapy: successful targeting and inhibition of the growth of the bladder cancer cells.
BACKGROUND
Virus-mediated gene therapy for bladder cancer has some problems, such as efficiency of gene delivery and safety issues. We have reported that poly-arginine peptide (11R) has the ability to increase protein transduction in cells. Here, we show that p53 protein transduction using 11R is useful for targeting to bladder tumors and suppressing the growth of bladder cancer cells.


METHODS
An 11R-fused p53 protein (11R-p53) was transduced in bladder cancer cell lines (J82 and T24) to evaluate the anti-tumor effect. Cell viability was assessed by performing the 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST) assay. To investigate whether 11R-p53 enhanced the effect on anti-cancer drug-dependent apoptosis of bladder cancer cells, the cell lines were cotreated with 11R-p53 and cis-diaminedichloroplatinum (CDDP). Apoptotic cells were identified using Hoechst staining. To investigate the efficiency of protein transduction mediated by 11R in bladder tumors in vivo, SCID mice were transplanted with J82 cells in the bladder and 11R-GFP was transurethrally transduced into the bladder. The transduction of 11R-GFP in the tumor was examined by confocal microscopy.


RESULTS
11R-p53 inhibited the growth of both J82 and T24 cells in a dose-dependent manner. The transduction of 11R-p53 enhanced CDDP-dependent induction of apoptosis. Transurethral application of 11R-GFP resulted in transduction of GFP in bladder tumors but not in the normal bladder epithelium or subepithelial tissues.


CONCLUSIONS
The present results suggest that p53 protein transduction therapy may be a promising method for the treatment of bladder cancer.
Inoue
Miyabi
M
Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
Tomizawa
Kazuhito
K
Matsushita
Masayuki
M
Lu
Yun-Fei
YF
Yokoyama
Teruhiko
T
Yanai
Hiroyuki
H
Takashima
Atsushi
A
Kumon
Hiromi
H
Matsui
Hideki
H
D015316:Genetic Therapy; D006801:Humans; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000627:therapeutic use*; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000628:therapy*
D016159:Tumor Suppressor Protein p53