title: Reinforcing B16F10/GPI-IL-21 vaccine efficacy against melanoma by injecting mice with shZEB1 plasmid or miR200c agomir.
abstract: In this study, we hypothesized that the inhibition of epithelial to mesenchymal transition (EMT) program by knockdown of Zinc-finger E-box binding homeobox 1 (ZEB1) or administration of miR200c agomir would strengthen the B16F10 cells transfected with GPI-anchored IL-21 (B16F10/GPI-IL-21) vaccine efficacy in inhibiting the melanoma metastasis. Our findings from the current study indicated that, when compared with the mice immunized with the B16F10/GPI-IL-21 vaccine alone, the mice immunized with B16F10/GPI-IL-21 vaccine combined with injection of shZEB1 plasmid or miR200c agomir not only meaningfully inhibited EMT of melanoma, reduced the EMT characteristic molecular expression in tumor tissues, but also significantly decreased the Treg cells and TGF-β1, enhanced the cytotoxicities of NK cells and cytotoxic T lymphocytes and the IFN-γ level. Furthermore, the immunotherapeutic combination resulted in inhibiting the melanoma growth and lung metastasis. Our study demonstrated that using the B16F10/GPI-IL-21 vaccine in combination with the down-regulated ZEB1 or miR200c administration effectively elicited anti-tumor immunity and reduced melanoma metastasis by inhibiting the EMT program in the B16F10 melanoma-bearing mice.
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing 210009, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing 210009, China.
authors.forename: Fengshu
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing 210009, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Shi
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing 210009, China; Department of Medical Oncology, Affiliated Tumor Hospital of Nantong University, Nantong 226361, China.
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing 210009, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Pan
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing 210009, China; Department of Gynecology & Obstetrics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing 210009, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing 210009, China; Department of Gynecology & Obstetrics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing 210009, China. Electronic address: njdoujun@seu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Dou
mesh_terms: D000818:Animals; D000070416:Antagomirs / Q000008:administration & dosage* / Q000378:metabolism; D015153:Blotting, Western; D019496:Cancer Vaccines / Q000276:immunology*; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D017261:Glycosylphosphatidylinositols / Q000276:immunology*; D007150:Immunohistochemistry; D007267:Injections; D007371:Interferon-gamma / Q000097:blood; D007378:Interleukins / Q000008:administration & dosage / Q000276:immunology*; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary; D008546:Melanoma, Experimental / Q000097:blood / Q000276:immunology*; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000276:immunology*; D010957:Plasmids / Q000008:administration & dosage / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000097:blood; D016896:Treatment Outcome; D014611:Vaccination; D000071799:Zinc Finger E-box-Binding Homeobox 1 / Q000378:metabolism*; D000098546:Interleukin-21
chemical_list: D000070416:Antagomirs; D019496:Cancer Vaccines; D017261:Glycosylphosphatidylinositols; D007378:Interleukins; D035683:MicroRNAs; C543719:Mirn200 microRNA, mouse; D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1; C519422:ZEB1 protein, mouse; D000071799:Zinc Finger E-box-Binding Homeobox 1; D007371:Interferon-gamma; D000098546:Interleukin-21
keywords: Interleukin-21; Melanoma; Tumor vaccine; Zinc-finger E-box binding homeobox 1; miR200c