A novel bladder cancer - specific oncolytic adenovirus by CD46 and its effect combined with cisplatin against cancer cells of CAR negative expression

  • Wenjuan Cao (Contributor)
  • Junqiang Tian (Contributor)
  • Chong Li (Creator)
  • Yanjun Gao (Contributor)
  • Xingchen Liu (Contributor)
  • Jian Zhong Lu (Contributor)
  • Yuhan Wang (Contributor)
  • Zhiping Wang (Contributor)
  • Robert Svatek (Creator)
  • Ronald Rodriguez (Creator)
  • Cao Wenjuan (Contributor)
  • Gao Yanjun (Contributor)
  • Liu Xingchen (Contributor)
  • Lu Jianzhong (Contributor)
  • Wang Zhiping (Contributor)



Abstract Background Conditionally replicative oncolytic adenoviruses (CRAds) display significant anti-tumor effects. However, the traditional adenovirus of serotype 5 (Ad5) entering cancer cells via coxsackie virus and adenovirus receptor (CAR) canâ t be utilized for bladder cancer with low expression of CAR, which limits the application of Ad5. Methods We utilized Ad5/F11p containing the chimeric fiber gene encoding the Ad5 fiber tail domain and Ad11p fiber shaft and knob domains to construct bladder cancer-specific chimeric type viruses Ad5/F11p-PSCAE-UPII-E1A, which can infect bladder cancer cells mediated by CD46 molecule. We carried out series of experiments in vitro to research anti-tumor effect of Ad5/F11p-PSCAE-UPII-E1A and the interaction in combination with cisplatin. Results The results demonstrated Ad5/F11p-PSCAE-UPII-E1A could infect bladder cancer cells (T24, EJ and 5637) in a CAR-independent way, and exert anti-tumor effect by blocking the cancer cells in G1 phase and inducing apoptosis. Ad5/F11p-PSCAE-UPII-E1A plus cisplatin enhanced the anti-proliferative effect and increased the number of apoptotic cells compared with viruses or cisplatin alone. Ad5/F11p-PSCAE-UPII-E1A plus cisplatin could upregulate the proteins expression of p53, Bax, and cleaved caspase-3, and downregulated Bcl-2 protein expression in T24, EJ and 5637 cells. Conclusion We constructed a bladder cancer-specific oncolytic adenovirus and provided new combination treatment strategies for bladder cancer.
Datos disponibles2017

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