Gene therapy for bladder cancer using E1B-55 kD-deleted adenovirus in combination with adenoviral vector encoding plasminogen kringles 1-5

J. L. Hsieh, C. L. Wu, M. D. Lai, C. H. Lee, C. S. Tsai, A. L. Shiau

研究成果: Article

10 引文 斯高帕斯(Scopus)

摘要

Mutations or loss of heterozygosity of p53 are detected in approximately 50% of bladder cancers. E1B-55 kD-deleted adenovirus has been shown to kill tumour cells with defective p53 function while sparing normal cells. Here, we examined the cytolytic effect and replication of E1B-55 kD-deleted adenovirus, designated Ad5WS1, on human bladder cancer cell lines with various p53 status. Ad5WS1 caused more severe cytolytic effect and replicated more efficiently in J82 and TCC-SUP bladder cancer cells carrying mutant p53 compared with TSGH-8301 and BFTC-905 bladder cancer cells retaining wild-type p53. Introduction of dominant negative p53 into BFTC-905 cells rendered them more susceptible to Ad5WS1-induced cytolysis. Furthermore, cells susceptible to lysis caused by Ad5WS1 were not attributable to their greater infectability by adenovirus. Finally, Ad5WS1 suppressed the growth of TCC-SUP bladder tumour xenografts, which could be augmented when combined with replication-defective adenoviral vector encoding kringles 1-5 of plasminogen (K1-5), an angiogenic inhibitor. Taken together, our results show that E1B-55 kD-deleted adenovirus replicates and hence lyses bladder cancer cells with mutant p53 much more efficient than those with wild-type p53. Thus, E1B-deleted adenovirus may have therapeutic potential, especially in combination with adenoviral vector expressing K1-5, for the treatment of bladder cancer.

原文English
頁(從 - 到)1492-1499
頁數8
期刊British Journal of Cancer
88
發行號9
DOIs
出版狀態Published - 2003 五月 6

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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