Tingyu Li1,2, Jinbo Fang1,2, Jihao Chu3, Xing Liu4, Yiquan Li1,2, Yilong Zhu1,2, Shanzhi Li1,2, Zhiru Xiu1, Yaru Li1, Ningyi Jin1,2,5, Guangzhe Zhu6, Lili Sun7, Xiao Li8,9,10. 1. Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Jingyue Economic and Technological Development Zone, No. 1035, Boshuo Road, Changchun, 130117, Jilin, People's Republic of China. 2. Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, People's Republic of China. 3. College of Life Sciences, Jilin University, Changchun, 130012, People's Republic of China. 4. Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, 130012, People's Republic of China. 5. Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, People's Republic of China. 6. Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Jingyue Economic and Technological Development Zone, No. 1035, Boshuo Road, Changchun, 130117, Jilin, People's Republic of China. zhuguangze820@126.com. 7. Department of Head and Neck Surgery, Tumor Hospital of Jilin Province, Changchun, 130012, People's Republic of China. linjiaxiaoya@163.com. 8. Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Jingyue Economic and Technological Development Zone, No. 1035, Boshuo Road, Changchun, 130117, Jilin, People's Republic of China. lixiao06@mails.jlu.edu.cn. 9. Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, People's Republic of China. lixiao06@mails.jlu.edu.cn. 10. Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, People's Republic of China. lixiao06@mails.jlu.edu.cn.
Abstract
PURPOSE: Oncolytic virotherapy is emerging as an important modality in cancer treatment. In a previous study, we designed and constructed Ad-Apoptin-hTERTp-E1a (Ad-VT), a dual cancer-selective anti-tumor recombinant adenovirus. METHODS: To explore the therapeutic effect of recombinant adenovirus Ad-VT together with Etoposide on small cell lung cancer, the ability of Ad-VT alone, Etoposide alone, and a combination of Ad-VT + Etoposide to inhibit proliferation of NCI-H446 and BEAS-2B cells was investigated using the WST-1 method. According to the inhibitory action of different combinations, a combination index (CI) was estimated by CalcuSyn software to select the best combination. The inhibitory effect of Ad-VT combined with Etoposide on NCI-H446 and BEAS-2B cells was detected by crystal violet staining and the CFST method. Hoechst, Annexin V and JC-1 staining were used to explore the inhibitory pathway of Ad-VT combined with Etoposide on NCI-H446 cells. The migratory and invasive abilities of treated NCI-H446 cells were assessed by Transwell and BioCat methods. Tumor volume, body weight and survival rate were measured to analyze the anti-tumor and toxic effects of different treatments in tumor-bearing mice. RESULTS: Ad-VT (20 MOI) combined with Etoposide (400 nM) significantly inhibited NCI-H446 cell proliferation with reduced toxicity of Etoposide to normal cells. Ad-VT induced apoptosis of NCI-H446 cells mainly through the mitochondrial apoptosis pathway, an effect significantly increased by the combined treatment. Ad-VT together with Etoposide significantly inhibited migration and invasion of NCI-H446 cells, inhibited tumor growth in vivo and prolonged the survival of tumor-bearing mice. CONCLUSIONS: The above results indicate that when combined with Etoposide, Ad-VT may have an important role in synergistically inhibiting tumors.
PURPOSE: Oncolytic virotherapy is emerging as an important modality in cancer treatment. In a previous study, we designed and constructed Ad-Apoptin-hTERTp-E1a (Ad-VT), a dual cancer-selective anti-tumor recombinant adenovirus. METHODS: To explore the therapeutic effect of recombinant adenovirus Ad-VT together with Etoposide on small cell lung cancer, the ability of Ad-VT alone, Etoposide alone, and a combination of Ad-VT + Etoposide to inhibit proliferation of NCI-H446 and BEAS-2B cells was investigated using the WST-1 method. According to the inhibitory action of different combinations, a combination index (CI) was estimated by CalcuSyn software to select the best combination. The inhibitory effect of Ad-VT combined with Etoposide on NCI-H446 and BEAS-2B cells was detected by crystal violet staining and the CFST method. Hoechst, Annexin V and JC-1 staining were used to explore the inhibitory pathway of Ad-VT combined with Etoposide on NCI-H446 cells. The migratory and invasive abilities of treated NCI-H446 cells were assessed by Transwell and BioCat methods. Tumor volume, body weight and survival rate were measured to analyze the anti-tumor and toxic effects of different treatments in tumor-bearing mice. RESULTS: Ad-VT (20 MOI) combined with Etoposide (400 nM) significantly inhibited NCI-H446 cell proliferation with reduced toxicity of Etoposide to normal cells. Ad-VT induced apoptosis of NCI-H446 cells mainly through the mitochondrial apoptosis pathway, an effect significantly increased by the combined treatment. Ad-VT together with Etoposide significantly inhibited migration and invasion of NCI-H446 cells, inhibited tumor growth in vivo and prolonged the survival of tumor-bearing mice. CONCLUSIONS: The above results indicate that when combined with Etoposide, Ad-VT may have an important role in synergistically inhibiting tumors.
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