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Interleukin 12 shows a better curative effect on lung cancer than paclitaxel and cisplatin doublet chemotherapy

BACKGROUND: Interleukin 12 (IL-12) is a cytokine that has been reported to exhibit potent tumoricidal effects in animal tumor models. A combined approach using Paclitaxel and platinum-based doublet chemotherapy is the most commonly used backbone regimen for treating lung cancer. Despite numerous stu...

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Autores principales: Yue, Ting, Zheng, Xiaodong, Dou, Yaling, Zheng, Xiaohu, Sun, Rui, Tian, Zhigang, Wei, Haiming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994391/
https://www.ncbi.nlm.nih.gov/pubmed/27549240
http://dx.doi.org/10.1186/s12885-016-2701-7
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author Yue, Ting
Zheng, Xiaodong
Dou, Yaling
Zheng, Xiaohu
Sun, Rui
Tian, Zhigang
Wei, Haiming
author_facet Yue, Ting
Zheng, Xiaodong
Dou, Yaling
Zheng, Xiaohu
Sun, Rui
Tian, Zhigang
Wei, Haiming
author_sort Yue, Ting
collection PubMed
description BACKGROUND: Interleukin 12 (IL-12) is a cytokine that has been reported to exhibit potent tumoricidal effects in animal tumor models. A combined approach using Paclitaxel and platinum-based doublet chemotherapy is the most commonly used backbone regimen for treating lung cancer. Despite numerous studies regarding the anti-tumor effects of IL-12 and the widespread use of conventional chemotherapy, few direct comparisons of IL-12 and conventional chemotherapy in the treatment of lung cancer have been performed. METHODS: We compared IL-12 to paclitaxel and cisplatin doublet chemotherapy in terms of efficacy against lung cancer in mouse models. The antitumor effect was measured by survival assays, histological analyses and imaging analyses. The cytokine levels were assessed using enzyme linked immunosorbent assay (ELISA) and flow cytometry (FACS). The spleen sizes were measured. CD31, CD105 and Vascular endothelial growth factor receptor 3 (VEGFR3) were analyzed using immunofluorescence. Matrix metalloprotein-9 (MMP-9) and cadherin 1 (CDH1) transcript levels were measured by quantitative PCR. Tumor cells apoptosis were examined by Tunel assay. RESULTS: The results showed that IL-12 treatment inhibited lung tumor growth, resulting in the long-term survival of lung cancer-bearing mice. Further examination revealed that IL-12 rapidly activated NK cells to secrete IFN-γ, resulting in the inhibition of tumor angiogenesis. In contrast, paclitaxel and cisplatin doublet chemotherapy did not show the expected efficacy in orthotopic lung cancer models; the IFN-γ levels were not increased after this treatment, and the number of peripheral lymphocytes was reduced. CONCLUSION: Together, these animal model data indicate that IL-12 shows a better curative effect than PTX + CDDP doublet chemotherapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2701-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-49943912016-08-24 Interleukin 12 shows a better curative effect on lung cancer than paclitaxel and cisplatin doublet chemotherapy Yue, Ting Zheng, Xiaodong Dou, Yaling Zheng, Xiaohu Sun, Rui Tian, Zhigang Wei, Haiming BMC Cancer Research Article BACKGROUND: Interleukin 12 (IL-12) is a cytokine that has been reported to exhibit potent tumoricidal effects in animal tumor models. A combined approach using Paclitaxel and platinum-based doublet chemotherapy is the most commonly used backbone regimen for treating lung cancer. Despite numerous studies regarding the anti-tumor effects of IL-12 and the widespread use of conventional chemotherapy, few direct comparisons of IL-12 and conventional chemotherapy in the treatment of lung cancer have been performed. METHODS: We compared IL-12 to paclitaxel and cisplatin doublet chemotherapy in terms of efficacy against lung cancer in mouse models. The antitumor effect was measured by survival assays, histological analyses and imaging analyses. The cytokine levels were assessed using enzyme linked immunosorbent assay (ELISA) and flow cytometry (FACS). The spleen sizes were measured. CD31, CD105 and Vascular endothelial growth factor receptor 3 (VEGFR3) were analyzed using immunofluorescence. Matrix metalloprotein-9 (MMP-9) and cadherin 1 (CDH1) transcript levels were measured by quantitative PCR. Tumor cells apoptosis were examined by Tunel assay. RESULTS: The results showed that IL-12 treatment inhibited lung tumor growth, resulting in the long-term survival of lung cancer-bearing mice. Further examination revealed that IL-12 rapidly activated NK cells to secrete IFN-γ, resulting in the inhibition of tumor angiogenesis. In contrast, paclitaxel and cisplatin doublet chemotherapy did not show the expected efficacy in orthotopic lung cancer models; the IFN-γ levels were not increased after this treatment, and the number of peripheral lymphocytes was reduced. CONCLUSION: Together, these animal model data indicate that IL-12 shows a better curative effect than PTX + CDDP doublet chemotherapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2701-7) contains supplementary material, which is available to authorized users. BioMed Central 2016-08-22 /pmc/articles/PMC4994391/ /pubmed/27549240 http://dx.doi.org/10.1186/s12885-016-2701-7 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Yue, Ting
Zheng, Xiaodong
Dou, Yaling
Zheng, Xiaohu
Sun, Rui
Tian, Zhigang
Wei, Haiming
Interleukin 12 shows a better curative effect on lung cancer than paclitaxel and cisplatin doublet chemotherapy
title Interleukin 12 shows a better curative effect on lung cancer than paclitaxel and cisplatin doublet chemotherapy
title_full Interleukin 12 shows a better curative effect on lung cancer than paclitaxel and cisplatin doublet chemotherapy
title_fullStr Interleukin 12 shows a better curative effect on lung cancer than paclitaxel and cisplatin doublet chemotherapy
title_full_unstemmed Interleukin 12 shows a better curative effect on lung cancer than paclitaxel and cisplatin doublet chemotherapy
title_short Interleukin 12 shows a better curative effect on lung cancer than paclitaxel and cisplatin doublet chemotherapy
title_sort interleukin 12 shows a better curative effect on lung cancer than paclitaxel and cisplatin doublet chemotherapy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994391/
https://www.ncbi.nlm.nih.gov/pubmed/27549240
http://dx.doi.org/10.1186/s12885-016-2701-7
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