Bladder cancer therapy using combined proliferating cell nuclear antigen antisense oligonucleotides and recombinant adenovirus p53.
OBJECTIVE
To evaluate the antitumor efficacy of proliferating cell nuclear antigen antisense oligonucleotide (PCNA-ASO) in combination with recombinant adenovirus p53 (Ad-p53) against bladder cancer EJ and BIU-87 cells in vitro and in vivo.


METHODS
Cells were transfected with Ad-p53 (100 MOI), and PCNA-ASO (1.6 micro mol/L) was then introduced into the cells using a cationic lipid (lipofectamine, 20 micro l/ml). In vitro and in vivo antitumor effects of combining PCNA-ASO with Ad-p53 were measured using the MTT assay, flow cytometry, clone formation, and a nude mice model.


RESULTS
The combination of PCNA-ASO and Ad-p53 inhibited cell viability in both the EJ (89.3%) and BIU-87 (78.6%) cell lines. The ability of the cells to form foci was also reduced by 74.8% in EJ cells and by 67.5% in BIU-87 cells (P < 0.01). A significant decrease of cells in the S phase (11.4% in EJ cells, 14.6% in BIU-87 cells) and a significant increase of cells in G1 phase (62.2% in EJ, 56.8% in BIU-87) were noted. The mean tumor volume after 7 days of treatment with PCNA-ASO or Ad-p53 in combination decreased to 47.6% or 36.4% of the initial tumor size in the two cell lines respectively.


CONCLUSIONS
These results indicate that combined PCNA-ASO and Ad-p53 in the treatment of bladder cancer with mutant p53 has important therapeutic potential, significantly suppressing the growth of human bladder cancer both in vitro and in vivo.
Zhu
Zhaohui
Z
Department of Urology, Union Hospital, Tongji Medical College, Huazhong Science and Technology University, Wuhan 430022, China. zhuzhaohui316@hotmail.com
Xing
Shian
S
Lin
Chen
C
Zhang
Xueyan
X
Fu
Ming
M
Liang
Xiao
X
Zeng
Fuqing
F
Lu
Gongcheng
G
Wu
Min
M
D000256:Adenoviridae; D000818:Animals; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage*; D018809:Proliferating Cell Nuclear Antigen / Q000008:administration & dosage*; D011994:Recombinant Proteins; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000008:administration & dosage*; D001749:Urinary Bladder Neoplasms / Q000628:therapy*
D016376:Oligonucleotides, Antisense; D018809:Proliferating Cell Nuclear Antigen; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53