{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T16:32:48Z","timestamp":1777480368819,"version":"3.51.4"},"reference-count":44,"publisher":"SAGE Publications","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CBM"],"published-print":{"date-parts":[[2021,11,10]]},"abstract":"<jats:p>BACKGROUND: To explore the suppressive effect of Apoptin-loaded oncolytic adenovirus (Ad-VT) on luciferase-labeled human melanoma cells in vitro and in vivo. METHODS: The stable luciferase-expressing human melanoma cells A375-luc or M14-luc were obtained by transfecting the plasmid pGL4.51 and selection with G418, followed by luciferase activity, genetic stability and bioluminescence intensity assays. In vitro, the inhibitory effects of Ad-VT on A375-luc or M14-luc were evaluated using the MTS cell proliferation, FITC-Annexin V apoptosis detection, transwell migration, Matrigel invasion and scratch assays. The inhibition pathway in Ad-VT-infected A375-luc and M14-luc cells were analyzed by JC-1 staining and Western-blot detection of mitochondrial apoptosis-related proteins. In vivo, the suppressive effects of Ad-VT on A375-luc or M14-luc were assessed by living imaging technology, tumor volume, bioluminescence intensity, survival curves and immunohistochemical analysis of the tumors from the xenograft tumor model BALB\/c nude mice. RESULTS: The growth and migration of A375-luc and M14-luc were significantly inhibited by Ad-VT in vitro. The evaluations of A375-luc and M14-luc tumor models in BALB\/c nude mice were successfully performed using living imaging technology. Ad-VT had an anti-tumor effect by reducing tumor growth and increasing survival in vivo. Ad-VT significantly changed the mitochondrial membrane potential by triggering the the mitochondrial release of apoptosis-related proteins, AIF (apoptosis inducing factor), ARTS (Apoptosis-Related Proteins), and Cyto-c (cytochrome c) from the mitochondria. CONCLUSION: Ad-VT reduced the mitochondrial membrane potential in A375-luc or M14-luc cells and induced the mitochondrial release of AIF, ARTS and Cyto-C. Ad-VT induced apoptosis in A375-luc or M14-luc cells via the mitochondrial apoptotic pathway.<\/jats:p>","DOI":"10.3233\/cbm-203150","type":"journal-article","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T13:53:09Z","timestamp":1629813189000},"page":"251-262","source":"Crossref","is-referenced-by-count":1,"title":["Suppression effect of a dual cancer-specific oncolytic adenovirus on luciferase-labeled human melanoma cells in vitro and in vivo"],"prefix":"10.1177","volume":"32","author":[{"given":"Min","family":"Li","sequence":"first","affiliation":[{"name":"Department of Dermatology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yilong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Academicians Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, Jilin, China"},{"name":"Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, Jilin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"Bai","sequence":"additional","affiliation":[{"name":"Academicians Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, Jilin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinbo","family":"Fang","sequence":"additional","affiliation":[{"name":"Academicians Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, Jilin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Yao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, Jilin, China"},{"name":"Center for Disease Control and Prevention, Agency for Offices Administration, Central Military Commission, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiquan","family":"Li","sequence":"additional","affiliation":[{"name":"Academicians Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, Jilin, China"},{"name":"Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, Jilin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanzhi","family":"Li","sequence":"additional","affiliation":[{"name":"Academicians Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, Jilin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Dermatology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China"},{"name":"Academicians Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, Jilin, China"},{"name":"Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, Jilin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ningyi","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Dermatology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China"},{"name":"Academicians Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, Jilin, China"},{"name":"Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, Jilin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rihua","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","reference":[{"key":"10.3233\/CBM-203150_ref1","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1089\/hum.2020.277","article-title":"Oncolytic adenovirus ORCA-010 activates proinflammatory myeloid cells and facilitates T cell recruitment and activation by PD-1 blockade in melanoma","volume":"32","author":"Milenova","year":"2021","journal-title":"Hum Gene Ther"},{"key":"10.3233\/CBM-203150_ref2","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1111\/cei.13442","article-title":"Oncolytic adenovirus ORCA-010 increases the type 1 T cell stimulatory capacity of melanoma-conditioned dendritic cells","volume":"201","author":"Lopez Gonzalez","year":"2020","journal-title":"Clin Exp Immunol"},{"key":"10.3233\/CBM-203150_ref3","doi-asserted-by":"crossref","first-page":"1874","DOI":"10.1038\/mt.2010.161","article-title":"Treatment of cancer patients with a serotype 5\/3 chimeric oncolytic adenovirus expressing GMCSF","volume":"18","author":"Koski","year":"2010","journal-title":"Mol Ther"},{"key":"10.3233\/CBM-203150_ref4","doi-asserted-by":"crossref","first-page":"2734","DOI":"10.1158\/1078-0432.CCR-12-2546","article-title":"Antiviral and antitumor T-cell immunity in patients treated with GM-CSF-coding oncolytic adenovirus","volume":"19","author":"Kanerva","year":"2013","journal-title":"Clin Cancer Res"},{"key":"10.3233\/CBM-203150_ref5","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1002\/ijc.29536","article-title":"Treatment of melanoma with a serotype 5\/3 chimeric oncolytic adenovirus coding for GM-CSF: results in vitro, in rodents and in humans","volume":"137","author":"Bramante","year":"2015","journal-title":"Int J Cancer"},{"key":"10.3233\/CBM-203150_ref6","doi-asserted-by":"crossref","unstructured":"B. Dreno, M. Urosevic-Maiwald, Y. Kim, J. Guitart, M. Duvic, O. Dereure, A. Khammari, A.C. Knol, A. Derbij, M. Lusky, I. Didillon, A.M. Santoni, B. Acres, V. Bataille, M.P. Chenard, P. Bleuzen, J.M. Limacher and R. Dummer, TG1042 (adenovirus-interferon-gamma) in primary cutaneous B-cell lymphomas: a phase II clinical trial, Plos One 9 (2014).","DOI":"10.1371\/journal.pone.0083670"},{"key":"10.3233\/CBM-203150_ref7","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1038\/mt.2010.52","article-title":"Phase II clinical trial of intratumoral application of TG1042 (adenovirus-interferon-gamma) in patients with advanced cutaneous T-cell lymphomas and multilesional cutaneous B-cell lymphomas","volume":"18","author":"Dummer","year":"2010","journal-title":"Molecular Therapy"},{"key":"10.3233\/CBM-203150_ref8","doi-asserted-by":"crossref","unstructured":"A. Khammari, J.M. Limacher, J.M. NGuyen, G. Quereux, A. Brocard, L. Peuvrel, A.C. Knol, S. Saiagh, V. Bataille and B. Dreno, Intra-lesional administrations of TG1042 (adenovirus expressing interferon-gamma) combined with adoptive TIL transfer in patients with metastatic melanoma, Journal of Clinical Oncology 30 (2012).","DOI":"10.1200\/jco.2012.30.15_suppl.e19019"},{"key":"10.3233\/CBM-203150_ref9","doi-asserted-by":"crossref","unstructured":"A. Khammari, J.M. Limacher, J.M. NGuyen, M. Saint-Jean, G. Quereux, A. Brocard, L. Peuvrel, A.C. Knol, S. Saiagh, V. Bataille and B. Dreno, Adoptive T-cell therapy combined with intra-lesional administrations of TG1042 (adenovirus expressing interferon-gamma) in metastatic melanoma patients, Journal of Clinical Oncology 31 (2013).","DOI":"10.1200\/jco.2013.31.15_suppl.e20022"},{"key":"10.3233\/CBM-203150_ref10","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1007\/s00262-015-1691-7","article-title":"Adoptive T cell therapy combined with intralesional administrations of TG1042 (adenovirus expressing interferon-gamma) in metastatic melanoma patients","volume":"64","author":"Khammari","year":"2015","journal-title":"Cancer Immunol Immunother"},{"key":"10.3233\/CBM-203150_ref11","doi-asserted-by":"crossref","first-page":"78573","DOI":"10.18632\/oncotarget.19750","article-title":"Local irradiation does not enhance the effect of immunostimulatory AdCD40L gene therapy combined with low dose cyclophosphamide in melanoma patients","volume":"8","author":"Irenaeus","year":"2017","journal-title":"Oncotarget"},{"key":"10.3233\/CBM-203150_ref12","doi-asserted-by":"crossref","first-page":"S247","DOI":"10.1016\/S1525-0016(16)35653-2","article-title":"AdCD40L immunostimulatory gene therapy in combination with cyclophosphamide prolongs 6-months survival in a phase I\/II trial for malignant melanoma","volume":"22","author":"Loskog","year":"2014","journal-title":"Molecular Therapy"},{"key":"10.3233\/CBM-203150_ref13","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1038\/bjc.2016.42","article-title":"Immunostimulatory AdCD40L gene therapy combined with low-dose cyclophosphamide in metastatic melanoma patients","volume":"114","author":"Loskog","year":"2016","journal-title":"British Journal of Cancer"},{"key":"10.3233\/CBM-203150_ref14","doi-asserted-by":"crossref","first-page":"S183","DOI":"10.1016\/S1525-0016(16)36274-8","article-title":"AdCD40L-from model systems to clinical trials for malignant melanoma","volume":"20","author":"Ullenhag","year":"2012","journal-title":"Molecular Therapy"},{"key":"10.3233\/CBM-203150_ref15","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1097\/CJI.0b013e31829d8a1b","article-title":"Treatment efficacy and immune stimulation by AdCD40L gene therapy of spontaneous canine malignant melanoma","volume":"36","author":"Westberg","year":"2013","journal-title":"Journal of Immunotherapy"},{"key":"10.3233\/CBM-203150_ref16","doi-asserted-by":"crossref","first-page":"23","DOI":"10.2174\/187153007780059432","article-title":"CD40L \u2013 a multipotent molecule for tumor therapy","volume":"7","author":"Loskog","year":"2007","journal-title":"Endocr Metab Immune Disord Drug Targets"},{"key":"10.3233\/CBM-203150_ref17","doi-asserted-by":"crossref","first-page":"3279","DOI":"10.1158\/1078-0432.CCR-10-0385","article-title":"AdCD40L immunogene therapy for bladder carcinoma \u2013 the first phase I\/IIa trial","volume":"16","author":"Malmstrom","year":"2010","journal-title":"Clin Cancer Res"},{"key":"10.3233\/CBM-203150_ref18","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/s12967-017-1182-z","article-title":"Adenovirus-mediated CD40L gene transfer increases teffector\/tregulatory cell ratio and upregulates death receptors in metastatic melanoma patients","volume":"15","author":"Schiza","year":"2017","journal-title":"J Transl Med"},{"key":"10.3233\/CBM-203150_ref19","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1038\/sj.mt.6300239","article-title":"Systemic toxicity-efficacy profile of ICOVIR-5, a potent and selective oncolytic adenovirus based on the pRB pathway","volume":"15","author":"Cascallo","year":"2007","journal-title":"Molecular Therapy"},{"key":"10.3233\/CBM-203150_ref20","first-page":"120","article-title":"A conditionally replicative adenovirus with enhanced infectivity shows improved oncolytic potency","volume":"7","author":"Suzuki","year":"2001","journal-title":"Clinical Cancer Research"},{"key":"10.3233\/CBM-203150_ref21","doi-asserted-by":"crossref","unstructured":"M. Garcia, R. Moreno, M. Gil, M. Cascallo, M.O. de Olza, C. Cuadra, J.M. Piulat, V. Navarro, M. Domenech, R. Alemany and R. Salazar, A phase I trial of oncolytic adenovirus ICOVIR-5 administered intravenously to cutaneous and uveal melanoma patients, Hum Gene Ther (2018).","DOI":"10.1089\/humc.2018.107"},{"key":"10.3233\/CBM-203150_ref22","doi-asserted-by":"crossref","unstructured":"X. Wang, L. Zhong and Y. Zhao, Oncolytic adenovirus: a tool for reversing the tumor microenvironment and promoting cancer treatment (review), Oncol Rep 45 (2021).","DOI":"10.3892\/or.2021.8000"},{"key":"10.3233\/CBM-203150_ref23","doi-asserted-by":"crossref","unstructured":"L. Tripodi, M. Vitale, V. Cerullo and L. Pastore, Oncolytic adenoviruses for cancer therapy, Int J Mol Sci 22 (2021).","DOI":"10.3390\/ijms22052517"},{"key":"10.3233\/CBM-203150_ref24","doi-asserted-by":"crossref","first-page":"e1490856","DOI":"10.1080\/2162402X.2018.1490856","article-title":"CD40L coding oncolytic adenovirus allows long-term survival of humanized mice receiving dendritic cell therapy","volume":"7","author":"Zafar","year":"2018","journal-title":"Oncoimmunology"},{"key":"10.3233\/CBM-203150_ref25","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1002\/1878-0261.12628","article-title":"A SIRPalpha-Fc fusion protein enhances the antitumor effect of oncolytic adenovirus against ovarian cancer","volume":"14","author":"Huang","year":"2020","journal-title":"Mol Oncol"},{"key":"10.3233\/CBM-203150_ref26","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1186\/s40425-019-0807-6","article-title":"Bi- and tri-valent T cell engagers deplete tumour-associated macrophages in cancer patient samples","volume":"7","author":"Scott","year":"2019","journal-title":"J Immunother Cancer"},{"key":"10.3233\/CBM-203150_ref27","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1002\/jmv.25229","article-title":"Antitumor-specific T-cell responses induced by oncolytic adenovirus ONCOS-102 (AdV5\/3-D24-GM-CSF) in peritoneal mesothelioma mouse model","volume":"90","author":"Kuryk","year":"2018","journal-title":"J Med Virol"},{"key":"10.3233\/CBM-203150_ref28","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s40425-019-0505-4","article-title":"Targeting the tumor stroma with an oncolytic adenovirus secreting a fibroblast activation protein-targeted bispecific T-cell engager","volume":"7","author":"de Sostoa","year":"2019","journal-title":"J Immunother Cancer"},{"key":"10.3233\/CBM-203150_ref29","doi-asserted-by":"crossref","unstructured":"X. Li, Y. Liu, Z.M. Wen, C. Li, H.J. Lu, M.Y. Tian, K.S. Jin, L.L. Sun, P. Gao, E.C. Yang, X.H. Xu, S.F. Kan, Z.Y. Wang, Y.H. Wang and N.Y. Jin, Potent anti-tumor effects of a dual specific oncolytic adenovirus expressing apoptin in vitro and in vivo, Molecular Cancer 9 (2010).","DOI":"10.1186\/1476-4598-9-10"},{"key":"10.3233\/CBM-203150_ref30","doi-asserted-by":"crossref","first-page":"10","DOI":"10.4161\/cbt.5.1.2400","article-title":"Cancer-selective therapy of the future \u2013 apoptin and its mechanism of action","volume":"5","author":"Maddika","year":"2006","journal-title":"Cancer Biology & Therapy"},{"key":"10.3233\/CBM-203150_ref31","doi-asserted-by":"crossref","first-page":"4805","DOI":"10.1093\/nar\/gkg661","article-title":"Apoptin protein multimers form distinct higher-order nucleoprotein complexes with DNA","volume":"31","author":"Leliveld","year":"2003","journal-title":"Nucleic Acids Research"},{"key":"10.3233\/CBM-203150_ref32","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.taap.2014.08.008","article-title":"Preclinical pharmacology and toxicology study of Ad-hTERT-E1a-Apoptin, a novel dual cancer-specific oncolytic adenovirus","volume":"280","author":"Qi","year":"2014","journal-title":"Toxicology and Applied Pharmacology"},{"key":"10.3233\/CBM-203150_ref33","doi-asserted-by":"crossref","first-page":"747","DOI":"10.3892\/ijmm.2012.1077","article-title":"Therapeutic efficacy of an hTERT promoter-driven oncolytic adenovirus that expresses apoptin in gastric carcinoma","volume":"30","author":"Liu","year":"2012","journal-title":"International Journal of Molecular Medicine"},{"key":"10.3233\/CBM-203150_ref34","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.3892\/ijo.2013.1783","article-title":"Potent growth-inhibitory effect of a dual cancer-specific oncolytic adenovirus expressing apoptin on prostate carcinoma","volume":"42","author":"Zhang","year":"2013","journal-title":"International Journal of Oncology"},{"key":"10.3233\/CBM-203150_ref35","first-page":"6275","article-title":"Synergistic antitumor effect of the combination of a dual cancer-specific oncolytic adenovirus and cisplatin on lung cancer cells","volume":"16","author":"Jin","year":"2018","journal-title":"Oncol Lett"},{"key":"10.3233\/CBM-203150_ref36","doi-asserted-by":"crossref","first-page":"S109","DOI":"10.1038\/515S109a","article-title":"Melanoma","volume":"515","author":"Owens","year":"2014","journal-title":"Nature"},{"key":"10.3233\/CBM-203150_ref37","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21590","article-title":"Cancer statistics, 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA Cancer J Clin"},{"key":"10.3233\/CBM-203150_ref38","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1245\/ASO.2005.06.004","article-title":"Is hepatic resection for large or multinodular hepatocellular carcinoma justified? Results from a multi-institutional database","volume":"12","author":"Ng","year":"2005","journal-title":"Ann Surg Oncol"},{"key":"10.3233\/CBM-203150_ref39","first-page":"11334","article-title":"Antitumor effects of apoptin expressed by the dual cancer-specific oncolytic adenovirus \u2013 a review","volume":"24","author":"Fang","year":"2020","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"10.3233\/CBM-203150_ref40","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.taap.2014.08.008","article-title":"Preclinical pharmacology and toxicology study of Ad-hTERT-E1a-Apoptin, a novel dual cancer-specific oncolytic adenovirus","volume":"280","author":"Qi","year":"2014","journal-title":"Toxicol Appl Pharmacol"},{"key":"10.3233\/CBM-203150_ref41","doi-asserted-by":"crossref","first-page":"3540","DOI":"10.2174\/0929867325666180309112023","article-title":"Apoptin, a versatile protein with selective antitumor activity","volume":"25","author":"Castro","year":"2018","journal-title":"Curr Med Chem"},{"key":"10.3233\/CBM-203150_ref42","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1002\/med.21626","article-title":"Therapeutic strategies for targeting telomerase in cancer","volume":"40","author":"Chen","year":"2020","journal-title":"Med Res Rev"},{"key":"10.3233\/CBM-203150_ref43","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1158\/2159-8290.CD-12-0503","article-title":"Illuminating cancer systems with genetically engineered mouse models and coupled luciferase reporters in vivo","volume":"3","author":"Kocher","year":"2013","journal-title":"Cancer Discov"},{"key":"10.3233\/CBM-203150_ref44","doi-asserted-by":"crossref","first-page":"180","DOI":"10.3390\/s110100180","article-title":"In vivo bioluminescent imaging (BLI): noninvasive visualization and interrogation of biological processes in living animals","volume":"11","author":"Close","year":"2011","journal-title":"Sensors (Basel)"}],"container-title":["Cancer Biomarkers"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/CBM-203150","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T14:08:19Z","timestamp":1777385299000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/CBM-203150"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,10]]},"references-count":44,"journal-issue":{"issue":"3"},"URL":"https:\/\/doi.org\/10.3233\/cbm-203150","relation":{},"ISSN":["1875-8592","1574-0153"],"issn-type":[{"value":"1875-8592","type":"electronic"},{"value":"1574-0153","type":"print"}],"subject":[],"published":{"date-parts":[[2021,11,10]]}}}