Antitumoral Effects Of The Recombinant Adenovirus On Cancer Cell In Vitro And In Vivo

Cancer incidence and mortality have been increasing in China, making cancer the leading cause of death and a major public health problem in the country. It is predicted that there will be about 4292,000 newly diagnosed cancer cases in China, and about 2814,000 Chinese will die from cancer in 2015. Surgery, chemotherapy, and radiotherapy are still the most common therapeutic options for cancer, but conventional chemotherapy can cause high toxicity due to the lack of specificity. It is necessary to improve and develop novel strategies for cancer therapy. Gene therapy provides a unique and powerful approach to combat cancer. However, how to effectively and safely deliver this therapeutic agent to human body has been a major challenge to gene therapists. Adenovirus has been the most common gene transfer vector for cancer gene therapy, oncolytic adenovirus represent a group of promising anti-cancer agents with the ability to lyse infected cancer cells but not normal cells. Apoptin is a protein encoded by the VP3 gene of CAV and selectively replicate in tumors, and HN is a surface protein of NDV and can induce apoptosis. Ad-VT(Ad-Apoptin-hTERTp-E1a) and Ad-HP(Ad-HN-PEG3p-E1a)are oncolytic adenovirus that expressed Apoptin and HN, the aim of this study is to elucidate whether the use of Ad-VT and Ad-HP would be an effective therapeutic strategy for cancer.Osteosarcoma cells and normal cells are treated with Ad-Apoptin-hTERTp-E1a(Ad-VT), and gastric cancer cell treated with Ad-HP(Ad-HN-PEG3p-E1a). Cellular proliferation inhibition rate was measured by MTT reduction assay. In vitro, morphological changes were detected by AO/EB staining and DAPI nuclear staining, apoptosis induction was detected by Annexin V/PI using flow cytometric analysis and staining, apoptotic pathway were detected by caspase assays. In vivo, to build mouse models and detected the tumor growth and mean survival.Ad-VT and Ad-HN-PEG3p-E1 a had anti-tumor effect on the growth of cells in a dose- and time-dependent manner, but. In vitro, Ad-VT and Ad-HN-PEG3p-E1 a could induce apoptosis of cancer cell and through activated caspase enzymes. In vivo, they could significantly slow the tumor growth and prolong the mean survival.These results uncover Ad-VT(Ad-Apoptin-hTERTp-E1a)and Ad-HP(Ad-HNPEG3p-E1a)as a promising strategy for cancer, setting the bases to propel a trial for patients with this disease.