title: A novel LMP1 antibody synergizes with mitomycin C to inhibit nasopharyngeal carcinoma growth in vivo through inducing apoptosis and downregulating vascular endothelial growth factor.
abstract: Combined therapy emerges as an attractive strategy for cancer treatment. The aim of this study was to investigate the inhibitory effects of mitomycin C (MMC) combined with a novel antibody fragment (Fab) targeting latent membrane protein 1 (LMP1) on nasopharyngeal carcinoma (NPC) xenograft nude mice. The inhibitory rates of MMC (2 mg/kg), Fab (4 mg/kg), MMC (2 mg/kg) + Fab (4 mg/kg), and MMC (1 mg/kg) + Fab (4 mg/kg) were 20.1%, 7.3%, 42.5% and 40.5%, respectively. Flow cytometry analysis showed that the apoptotic rate of xenograft tumor cells in the MMC and Fab combination group was 28 ± 4.12%, significantly higher than the MMC (2 mg/kg) group (P < 0.01). Immunohistochemical staining showed that VEGF expression in NPC xenografts was significantly inhibited in the combination group compared to the Fab (4 mg/kg) group (P < 0.05). In conclusion, both MMC and Fab could inhibit NPC xenograft tumor growth in vivo and combination therapy showed apparent synergistic anti-tumor effects, which may be due to the induction of tumor cell apoptosis and the downregulation of VEGF expression. These results suggest that the novel combined therapy utilizing traditional chemotherapeutics and antibody-targeted therapy could be a promising strategy for the treatment of NPC.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan, Nanjing 210011, China.|Department of Otolaryngology-Head and Neck Surgery, Jiangsu Province Official Hospital, 65 Jiangsu Road, 210029 Nanjing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan, Nanjing 210011, China.
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Zhang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan, Nanjing 210011, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wen
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan, Nanjing 210011, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Cao
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan, Nanjing 210011, China.|The Key Laboratory of Cancer Biomarkers, Prevention & Treatment Cancer Center and The Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, China.
authors.forename: Ren-Jie
authors.initials: RJ
authors.lastname: Chen
authors.affiliation: The Key Laboratory of Cancer Biomarkers, Prevention & Treatment Cancer Center and The Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, China.|Huadong Medical Institute of Biotechniques, 293 Zhongshandong Road, Nanjing 210002, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhu
authors.affiliation: The Key Laboratory of Cancer Biomarkers, Prevention & Treatment Cancer Center and The Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, China.
authors.forename: Zhen-Qing
authors.initials: ZQ
authors.lastname: Feng
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002277:Carcinoma; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016685:Mitomycin / Q000494:pharmacology*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000037:antagonists & inhibitors / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000906:Antibodies; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D042461:Vascular Endothelial Growth Factor A; D014763:Viral Matrix Proteins; D016685:Mitomycin