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A new oncolytic adenoviral vector carrying dual tumour suppressor genes shows potent anti-tumour effect.

Liu XR, Cai Y, Cao X, Wei RC, Li HL, Zhou XM, Zhang KJ, Wu S, Qian QJ, Cheng B, Huang K, Liu XY - J. Cell. Mol. Med. (2012)

Bottom Line: Compared with the original ZD55 vector, this new adenoviral vector (ZD55SP/E1A) showed much better ability of replication and reporter gene expression.Our results demonstrated excellent anti-tumour effect of ZD55SP/E1A-IL-24-shMPP1 in vitro on multiple cancer cell lines such as lung cancer, liver cancer and ovarian caner.More importantly, ZD55SP/E1A-IL-24-shMPP1 also showed excellent anti-tumour effects in vivo on SW620 xenograft nude mice.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

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Characterization of the OV ZD55SP/E1A. (A) A schematic drawing of the oncolytic Ad ZD55SP/E1A-IL-24-shMPP1. Ψ is the encapsidation signal; ITR is the inverted terminal repeat. (B) Analysis of the replication ability of ZD55SP/E1A and ZD55 in the normal (MRC-5) and tumour cells (SW620 and HeLa) by RT-PCR. The adenovirus E3 region was amplified to evaluate the viral DNA content at 48 hrs after infection (MOI ∇ 0.1). Data are presented as mean ± S.D. (bars) (n ∇ 3, ***P < 0.001). (C–E) EGFP as a reporter gene. Normal-MRC-5 (C) and tumour cells A549 (D) or SW620 cells (E) were infected with ZD55SP/E1A-EGFP and ZD55-EGFP at an MOI of 0.2. EGFP expression was assessed by photomicrographic examination at 24 and 96 hrs after infection.
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fig03: Characterization of the OV ZD55SP/E1A. (A) A schematic drawing of the oncolytic Ad ZD55SP/E1A-IL-24-shMPP1. Ψ is the encapsidation signal; ITR is the inverted terminal repeat. (B) Analysis of the replication ability of ZD55SP/E1A and ZD55 in the normal (MRC-5) and tumour cells (SW620 and HeLa) by RT-PCR. The adenovirus E3 region was amplified to evaluate the viral DNA content at 48 hrs after infection (MOI ∇ 0.1). Data are presented as mean ± S.D. (bars) (n ∇ 3, ***P < 0.001). (C–E) EGFP as a reporter gene. Normal-MRC-5 (C) and tumour cells A549 (D) or SW620 cells (E) were infected with ZD55SP/E1A-EGFP and ZD55-EGFP at an MOI of 0.2. EGFP expression was assessed by photomicrographic examination at 24 and 96 hrs after infection.

Mentions: The OV ZD55SP/E1A is constructed based on the ZD55 vector [17]. In this study, the E1A promoter in the original wild-type serotype 5 Ad was replaced by the short 269 bp survivin promoter, and the E1B55KD was also deleted. Expression cassettes of both IL-24 and shMPP1 were then inserted into this new vector (Fig. 3A).


A new oncolytic adenoviral vector carrying dual tumour suppressor genes shows potent anti-tumour effect.

Liu XR, Cai Y, Cao X, Wei RC, Li HL, Zhou XM, Zhang KJ, Wu S, Qian QJ, Cheng B, Huang K, Liu XY - J. Cell. Mol. Med. (2012)

Characterization of the OV ZD55SP/E1A. (A) A schematic drawing of the oncolytic Ad ZD55SP/E1A-IL-24-shMPP1. Ψ is the encapsidation signal; ITR is the inverted terminal repeat. (B) Analysis of the replication ability of ZD55SP/E1A and ZD55 in the normal (MRC-5) and tumour cells (SW620 and HeLa) by RT-PCR. The adenovirus E3 region was amplified to evaluate the viral DNA content at 48 hrs after infection (MOI ∇ 0.1). Data are presented as mean ± S.D. (bars) (n ∇ 3, ***P < 0.001). (C–E) EGFP as a reporter gene. Normal-MRC-5 (C) and tumour cells A549 (D) or SW620 cells (E) were infected with ZD55SP/E1A-EGFP and ZD55-EGFP at an MOI of 0.2. EGFP expression was assessed by photomicrographic examination at 24 and 96 hrs after infection.
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Related In: Results  -  Collection

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fig03: Characterization of the OV ZD55SP/E1A. (A) A schematic drawing of the oncolytic Ad ZD55SP/E1A-IL-24-shMPP1. Ψ is the encapsidation signal; ITR is the inverted terminal repeat. (B) Analysis of the replication ability of ZD55SP/E1A and ZD55 in the normal (MRC-5) and tumour cells (SW620 and HeLa) by RT-PCR. The adenovirus E3 region was amplified to evaluate the viral DNA content at 48 hrs after infection (MOI ∇ 0.1). Data are presented as mean ± S.D. (bars) (n ∇ 3, ***P < 0.001). (C–E) EGFP as a reporter gene. Normal-MRC-5 (C) and tumour cells A549 (D) or SW620 cells (E) were infected with ZD55SP/E1A-EGFP and ZD55-EGFP at an MOI of 0.2. EGFP expression was assessed by photomicrographic examination at 24 and 96 hrs after infection.
Mentions: The OV ZD55SP/E1A is constructed based on the ZD55 vector [17]. In this study, the E1A promoter in the original wild-type serotype 5 Ad was replaced by the short 269 bp survivin promoter, and the E1B55KD was also deleted. Expression cassettes of both IL-24 and shMPP1 were then inserted into this new vector (Fig. 3A).

Bottom Line: Compared with the original ZD55 vector, this new adenoviral vector (ZD55SP/E1A) showed much better ability of replication and reporter gene expression.Our results demonstrated excellent anti-tumour effect of ZD55SP/E1A-IL-24-shMPP1 in vitro on multiple cancer cell lines such as lung cancer, liver cancer and ovarian caner.More importantly, ZD55SP/E1A-IL-24-shMPP1 also showed excellent anti-tumour effects in vivo on SW620 xenograft nude mice.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

Show MeSH
Related in: MedlinePlus