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Antitumor effects of nadroparin combined with radiotherapy in Lewis lung cancer models

BACKGROUND: The beneficial antitumor effects of low-molecular-weight heparins (LMWHs) have previously been investigated in basic and clinical studies. In this study, the antitumor efficacy of nadroparin combined with radiotherapy was investigated in vivo. METHODS: A total of 48 tumor-bearing mice we...

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Autores principales: Zhuang, Xibing, Qiao, Tiankui, Yuan, Sujuan, Zhang, Qi, Chen, Wei, Luo, Youjun, Xu, Guoxiong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6114476/
https://www.ncbi.nlm.nih.gov/pubmed/30210234
http://dx.doi.org/10.2147/OTT.S176526
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author Zhuang, Xibing
Qiao, Tiankui
Yuan, Sujuan
Zhang, Qi
Chen, Wei
Luo, Youjun
Xu, Guoxiong
author_facet Zhuang, Xibing
Qiao, Tiankui
Yuan, Sujuan
Zhang, Qi
Chen, Wei
Luo, Youjun
Xu, Guoxiong
author_sort Zhuang, Xibing
collection PubMed
description BACKGROUND: The beneficial antitumor effects of low-molecular-weight heparins (LMWHs) have previously been investigated in basic and clinical studies. In this study, the antitumor efficacy of nadroparin combined with radiotherapy was investigated in vivo. METHODS: A total of 48 tumor-bearing mice were randomly divided into six groups (n=8 per group): control group, irradiation group (X), LMWH(1,000) group, LMWH(2,000) group, LMWH(1,000)+X group and LMWH(2,000)+X group. Following this, tumor growth, weight and inhibitory rate, as well as the survival of mice in each group, were determined. Levels of serum interleukin (IL)-6 and transforming growth factor (TGF)-β1 were determined via enzyme-linked immunosorbent assay (ELISA) analyses. The expression levels of CD34 were investigated using immunohistochemistry analyses to represent the microvascular density (MVD) values of tumor tissues. In addition, tumor cell apoptosis was investigated using TdT-mediated dUTP nick end labeling (TUNEL) analysis post treatment. The expression levels of survivin were analyzed by Western blotting. RESULTS: The volumes and weights of tumors in the treatment groups were demonstrated to be significantly decreased, which was most obvious in the LMWH(2,000)+X group. The tumor inhibitory rate was significantly increased in the treated mice. ELISA assays demonstrated that the concentrations of serum IL-6 and TGF-β1 were significantly decreased in the LMWH(2,000)+X group. In addition, the decreased CD34 expression was found in the combined treatment groups. TUNEL assays demonstrated that the apoptosis rate was increased in treated mice, and the highest apoptosis rate was exhibited by the LMWH(2,000)+X group. Results of Western blotting demonstrated that combinatory treatment with both nadroparin and X-ray irradiation significantly inhibited the expression of survivin. CONCLUSION: These results demonstrated that a combinatory treatment strategy of nadroparin with fractionated irradiation had a strong synergistic antitumor effect in vivo, which may be associated with the promotion of apoptosis, inhibited secretion of TGF-β1 and IL-6 and down-regulation of CD34 and survivin expression.
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spelling pubmed-61144762018-09-12 Antitumor effects of nadroparin combined with radiotherapy in Lewis lung cancer models Zhuang, Xibing Qiao, Tiankui Yuan, Sujuan Zhang, Qi Chen, Wei Luo, Youjun Xu, Guoxiong Onco Targets Ther Original Research BACKGROUND: The beneficial antitumor effects of low-molecular-weight heparins (LMWHs) have previously been investigated in basic and clinical studies. In this study, the antitumor efficacy of nadroparin combined with radiotherapy was investigated in vivo. METHODS: A total of 48 tumor-bearing mice were randomly divided into six groups (n=8 per group): control group, irradiation group (X), LMWH(1,000) group, LMWH(2,000) group, LMWH(1,000)+X group and LMWH(2,000)+X group. Following this, tumor growth, weight and inhibitory rate, as well as the survival of mice in each group, were determined. Levels of serum interleukin (IL)-6 and transforming growth factor (TGF)-β1 were determined via enzyme-linked immunosorbent assay (ELISA) analyses. The expression levels of CD34 were investigated using immunohistochemistry analyses to represent the microvascular density (MVD) values of tumor tissues. In addition, tumor cell apoptosis was investigated using TdT-mediated dUTP nick end labeling (TUNEL) analysis post treatment. The expression levels of survivin were analyzed by Western blotting. RESULTS: The volumes and weights of tumors in the treatment groups were demonstrated to be significantly decreased, which was most obvious in the LMWH(2,000)+X group. The tumor inhibitory rate was significantly increased in the treated mice. ELISA assays demonstrated that the concentrations of serum IL-6 and TGF-β1 were significantly decreased in the LMWH(2,000)+X group. In addition, the decreased CD34 expression was found in the combined treatment groups. TUNEL assays demonstrated that the apoptosis rate was increased in treated mice, and the highest apoptosis rate was exhibited by the LMWH(2,000)+X group. Results of Western blotting demonstrated that combinatory treatment with both nadroparin and X-ray irradiation significantly inhibited the expression of survivin. CONCLUSION: These results demonstrated that a combinatory treatment strategy of nadroparin with fractionated irradiation had a strong synergistic antitumor effect in vivo, which may be associated with the promotion of apoptosis, inhibited secretion of TGF-β1 and IL-6 and down-regulation of CD34 and survivin expression. Dove Medical Press 2018-08-24 /pmc/articles/PMC6114476/ /pubmed/30210234 http://dx.doi.org/10.2147/OTT.S176526 Text en © 2018 Zhuang et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Zhuang, Xibing
Qiao, Tiankui
Yuan, Sujuan
Zhang, Qi
Chen, Wei
Luo, Youjun
Xu, Guoxiong
Antitumor effects of nadroparin combined with radiotherapy in Lewis lung cancer models
title Antitumor effects of nadroparin combined with radiotherapy in Lewis lung cancer models
title_full Antitumor effects of nadroparin combined with radiotherapy in Lewis lung cancer models
title_fullStr Antitumor effects of nadroparin combined with radiotherapy in Lewis lung cancer models
title_full_unstemmed Antitumor effects of nadroparin combined with radiotherapy in Lewis lung cancer models
title_short Antitumor effects of nadroparin combined with radiotherapy in Lewis lung cancer models
title_sort antitumor effects of nadroparin combined with radiotherapy in lewis lung cancer models
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6114476/
https://www.ncbi.nlm.nih.gov/pubmed/30210234
http://dx.doi.org/10.2147/OTT.S176526
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