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

Wenjuan Cao, Junqiang Tian, Chong Li, Yanjun Gao, Xingchen Liu, Jianzhong Lu, Yuhan Wang, Zhiping Wang, Robert Svatek, Ronald Rodriguez

Research output: Contribution to journalArticle

2 Citations (Scopus)

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) can'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.

Original languageEnglish (US)
Article number149
JournalVirology Journal
Volume14
Issue number1
DOIs
StatePublished - Aug 8 2017

Fingerprint

Coxsackie and Adenovirus Receptor-Like Membrane Protein
Virus Receptors
Enterovirus
Urinary Bladder Neoplasms
Adenoviridae
Cisplatin
Neoplasms
Viruses
Serogroup
G1 Phase
Caspase 3

Keywords

  • Apoptosis
  • Bladder cancer
  • Cisplatin
  • Coxsackie virus and adenovirus receptor
  • Oncolytic adenoviruses

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

Cite this

A novel bladder cancer - Specific oncolytic adenovirus by CD46 and its effect combined with cisplatin against cancer cells of CAR negative expression. / Cao, Wenjuan; Tian, Junqiang; Li, Chong; Gao, Yanjun; Liu, Xingchen; Lu, Jianzhong; Wang, Yuhan; Wang, Zhiping; Svatek, Robert; Rodriguez, Ronald.

In: Virology Journal, Vol. 14, No. 1, 149, 08.08.2017.

Research output: Contribution to journalArticle

Cao, Wenjuan ; Tian, Junqiang ; Li, Chong ; Gao, Yanjun ; Liu, Xingchen ; Lu, Jianzhong ; Wang, Yuhan ; Wang, Zhiping ; Svatek, Robert ; Rodriguez, Ronald. / A novel bladder cancer - Specific oncolytic adenovirus by CD46 and its effect combined with cisplatin against cancer cells of CAR negative expression. In: Virology Journal. 2017 ; Vol. 14, No. 1.
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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) can'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.",
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AU - Cao, Wenjuan

AU - Tian, Junqiang

AU - Li, Chong

AU - Gao, Yanjun

AU - Liu, Xingchen

AU - Lu, Jianzhong

AU - Wang, Yuhan

AU - Wang, Zhiping

AU - Svatek, Robert

AU - Rodriguez, Ronald

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AB - 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) can'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.

KW - Apoptosis

KW - Bladder cancer

KW - Cisplatin

KW - Coxsackie virus and adenovirus receptor

KW - Oncolytic adenoviruses

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