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Anti-tumor effects of a dual cancer-specific oncolytic adenovirus carried Apoptin and PEG3 promoter on colorectal cancer in vitro and in vivo
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Abstract:
Objective : To investigate the anti-tumor effects of a dual cancer-specific oncolytic adenovirus Ad-Apoptin-PEG3p-E1a on colorectal cancer in vitro and in vivo. Methods: A dual cancer-specific oncolytic adenovirus vector carried Apoptin and PEG3 promoter (Ad-Apoptin-PEG3p-E1a) was constructed. In experiments in vitro, colon cancer SW1116 cells and gastric epithelial GES cells were infected with the constructed adenoviral vector. At various time points after infection, cell viability was assessed by MTT assay, apoptosis, levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and cytochrome C (Cyt C) by flow cytometry. In experiments in vivo, BALB/c mice bearing established subcutaneous transplantation tumors were treated with Ad-Apoptin-PEG3p-E1a and a control vector respectively. Tumor growth kinetics and mean survival time were assessed. Results: In vitro, Ad-Apoptin-PEG3p-E1a significantly suppressed proliferation, increased ROS production, reduced MMP levels and enhanced Cyt C release in a dose- and time-dependent manner in SW1116 cells, as compared with the control vector. Ad-Apoptin-PEG3p-E1a infection also resulted in increased apoptosis in SW1116 cells but had no significant effects on GES cells. In vivo, Ad-Apoptin-PEG3p-E1a inhibited the growth of subcutaneous transplantation tumors significantly and extended the lifespan of the animals (41.0±07 days), while Ad-PEG3p-E1a-, Ad-Apoptin- and Ad-mock-treated animals had shorter mean survival time (34.4±16 days, 33.2±1.2 and 28.4±1.4, respectively, P<0.05）. Conclusion: The dual cancer-specific oncolytic adenovirus vector carrying Apoptin and PEG3p may offer a promising gene therapy for colon cancer.
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Project Supported:
Project supported by the National Natural Science Foundation of China（No. 81101140），the Grants from the National Science and Technology Major Project（No. 2014ZX09304314-002），the National High-Technology Research and Development Project of China（863 project）（No. 2012AA02A407）, and the Key Program of Science and Technology from Jilin Province（No. 20130206041NY）
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