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Mannose Impairs Lung Adenocarcinoma Growth and Enhances the Sensitivity of A549 Cells to Carboplatin

INTRODUCTION: Mannose, a major monosaccharide component of N-glycans, involves in the glycometabolism of human body. Recently, mannose has been shown to suppress tumor growth through enhancing chemosensitivity and reducing the activity of mannose phosphate isomerase (MPI). However, it is largely unk...

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Autores principales: Sha, Jun, Cao, Dandan, Cui, Rui, Xia, Lu, Hua, Xin, Lu, Yuan, Han, Shuhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648561/
https://www.ncbi.nlm.nih.gov/pubmed/33173340
http://dx.doi.org/10.2147/CMAR.S278673
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author Sha, Jun
Cao, Dandan
Cui, Rui
Xia, Lu
Hua, Xin
Lu, Yuan
Han, Shuhua
author_facet Sha, Jun
Cao, Dandan
Cui, Rui
Xia, Lu
Hua, Xin
Lu, Yuan
Han, Shuhua
author_sort Sha, Jun
collection PubMed
description INTRODUCTION: Mannose, a major monosaccharide component of N-glycans, involves in the glycometabolism of human body. Recently, mannose has been shown to suppress tumor growth through enhancing chemosensitivity and reducing the activity of mannose phosphate isomerase (MPI). However, it is largely unknown whether mannose exerts effects on non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: First, a mannose IC50 assay was conducted to find a suitable concentration of mannose for cell experiments. Then, vitro studies including CCK-8 assay, scratch wound healing assay, and TUNEL assay were performed to evaluate the effects of mannose on A549 cells, and an animal model was established to evaluate the antitumoural effect of mannose on NSCLC in vivo. Finally, immunohistochemistry was done to detect the expression of MPI by Rabbit Anti-MPI. RESULTS: In this study, a concentration of mannose, 15mM, was used to explore the suppressive effect of mannose on A549 cells. CCK-8 assay demonstrated that mannose significantly inhibited the proliferation of A549 cells and enhanced the anti-tumor efficacy of carboplatin. Wound healing assay showed that mannose inhibits the migration of A549 cells, and mannose-induced migration inhibition was more efficient in A549 cells treated with carboplatin. TUNEL assay demonstrated that mannose significantly enhanced the efficacy of carboplatin to promote apoptosis treated by mannose (15mM) or carboplatin. The results of animal experiments revealed that the size and weight of tumors derived from A549 cells treated with mannose were smaller than those derived from control cells, and co-treatment with mannose and carboplatin had most efficient inhibition on tumor growth. MPI expression detection showed that the expression level of MPI in the stage Tis (tumor in situ) was the highest, while the stage IV has the lowest. DISCUSSION: Collectively, our findings suggest that mannose inhibited cell proliferation and migration, promoted cell apoptosis and enhanced the efficacy of carboplatin in lung adenocarcinoma. Preliminary results showed that mannose had less side effect on health. In the future, mannose may be a potential candidate drug for adjuvant therapy of lung adenocarcinoma.
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spelling pubmed-76485612020-11-09 Mannose Impairs Lung Adenocarcinoma Growth and Enhances the Sensitivity of A549 Cells to Carboplatin Sha, Jun Cao, Dandan Cui, Rui Xia, Lu Hua, Xin Lu, Yuan Han, Shuhua Cancer Manag Res Original Research INTRODUCTION: Mannose, a major monosaccharide component of N-glycans, involves in the glycometabolism of human body. Recently, mannose has been shown to suppress tumor growth through enhancing chemosensitivity and reducing the activity of mannose phosphate isomerase (MPI). However, it is largely unknown whether mannose exerts effects on non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: First, a mannose IC50 assay was conducted to find a suitable concentration of mannose for cell experiments. Then, vitro studies including CCK-8 assay, scratch wound healing assay, and TUNEL assay were performed to evaluate the effects of mannose on A549 cells, and an animal model was established to evaluate the antitumoural effect of mannose on NSCLC in vivo. Finally, immunohistochemistry was done to detect the expression of MPI by Rabbit Anti-MPI. RESULTS: In this study, a concentration of mannose, 15mM, was used to explore the suppressive effect of mannose on A549 cells. CCK-8 assay demonstrated that mannose significantly inhibited the proliferation of A549 cells and enhanced the anti-tumor efficacy of carboplatin. Wound healing assay showed that mannose inhibits the migration of A549 cells, and mannose-induced migration inhibition was more efficient in A549 cells treated with carboplatin. TUNEL assay demonstrated that mannose significantly enhanced the efficacy of carboplatin to promote apoptosis treated by mannose (15mM) or carboplatin. The results of animal experiments revealed that the size and weight of tumors derived from A549 cells treated with mannose were smaller than those derived from control cells, and co-treatment with mannose and carboplatin had most efficient inhibition on tumor growth. MPI expression detection showed that the expression level of MPI in the stage Tis (tumor in situ) was the highest, while the stage IV has the lowest. DISCUSSION: Collectively, our findings suggest that mannose inhibited cell proliferation and migration, promoted cell apoptosis and enhanced the efficacy of carboplatin in lung adenocarcinoma. Preliminary results showed that mannose had less side effect on health. In the future, mannose may be a potential candidate drug for adjuvant therapy of lung adenocarcinoma. Dove 2020-11-03 /pmc/articles/PMC7648561/ /pubmed/33173340 http://dx.doi.org/10.2147/CMAR.S278673 Text en © 2020 Sha et al. http://creativecommons.org/licenses/by-nc/3.0/ 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. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Sha, Jun
Cao, Dandan
Cui, Rui
Xia, Lu
Hua, Xin
Lu, Yuan
Han, Shuhua
Mannose Impairs Lung Adenocarcinoma Growth and Enhances the Sensitivity of A549 Cells to Carboplatin
title Mannose Impairs Lung Adenocarcinoma Growth and Enhances the Sensitivity of A549 Cells to Carboplatin
title_full Mannose Impairs Lung Adenocarcinoma Growth and Enhances the Sensitivity of A549 Cells to Carboplatin
title_fullStr Mannose Impairs Lung Adenocarcinoma Growth and Enhances the Sensitivity of A549 Cells to Carboplatin
title_full_unstemmed Mannose Impairs Lung Adenocarcinoma Growth and Enhances the Sensitivity of A549 Cells to Carboplatin
title_short Mannose Impairs Lung Adenocarcinoma Growth and Enhances the Sensitivity of A549 Cells to Carboplatin
title_sort mannose impairs lung adenocarcinoma growth and enhances the sensitivity of a549 cells to carboplatin
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648561/
https://www.ncbi.nlm.nih.gov/pubmed/33173340
http://dx.doi.org/10.2147/CMAR.S278673
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