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Intratumorally CpG immunotherapy with carbon nanotubes inhibits local tumor growth and liver metastasis by suppressing the epithelial–mesenchymal transition of colon cancer cells
Colon cancer liver metastasis accounts for the major cause of death of colon cancer patients. Previous study reported a carbon nanotubes (CNT)-conjugated CpG complex (CNT-CpG), which displayed a significant antitumor effect in gliomas. However, whether CNT-CpG could limit colon tumor growth and supp...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861496/ https://www.ncbi.nlm.nih.gov/pubmed/32976213 http://dx.doi.org/10.1097/CAD.0000000000001000 |
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author | Jin, Hongyong Gao, Sujie Song, Defeng Liu, Yiting Chen, Xuebo |
author_facet | Jin, Hongyong Gao, Sujie Song, Defeng Liu, Yiting Chen, Xuebo |
author_sort | Jin, Hongyong |
collection | PubMed |
description | Colon cancer liver metastasis accounts for the major cause of death of colon cancer patients. Previous study reported a carbon nanotubes (CNT)-conjugated CpG complex (CNT-CpG), which displayed a significant antitumor effect in gliomas. However, whether CNT-CpG could limit colon tumor growth and suppress the colon cancer liver metastasis has not been evaluated. In this study, we report CNT enhances CpG uptake in mouse colon cancer cells. Results demonstrated only CpG with CNT conjugation showed significant activation of NF-κB signal. Moreover, intratumorally delivery of CNT-CpG successfully suppressed local xenograft tumor growth and liver metastasis. CNT-CpG treatments cured 75% of mice and inhibited local tumor growth, significantly prolonged survival outcomes and limited liver metastatic tumor nodules from colon cancer cells. Using human colon cancer cell line, HCT116, we observed significantly inhibitory effects of CNT-CpG on cell growth, invasion and migration. Importantly, CNT-CpG treatment blocked the epithelial to mesenchymal transition (EMT). We compared the mRNA levels of EMT markers of colon cancer cells without or with CNT-CpG treatment from in-vitro and in-vivo models. Consistent results demonstrated expression of epithelial marker, E-cadherin was upregulated by CNT-CpG. In contrast, three mesenchymal markers, snail, fibronectin and vimentin were significantly suppressed by CNT-CpG treatment compared with control or free CpG. In summary, our data suggest CNT-CpG is an effective therapeutic approach against local colon tumor and their liver metastasis. This study presents the CNT-CpG complex as a promising therapeutic target for developing novel therapies against both local colon tumors and liver metastatic tumors. |
format | Online Article Text |
id | pubmed-7861496 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-78614962021-02-11 Intratumorally CpG immunotherapy with carbon nanotubes inhibits local tumor growth and liver metastasis by suppressing the epithelial–mesenchymal transition of colon cancer cells Jin, Hongyong Gao, Sujie Song, Defeng Liu, Yiting Chen, Xuebo Anticancer Drugs Preclinical Reports Colon cancer liver metastasis accounts for the major cause of death of colon cancer patients. Previous study reported a carbon nanotubes (CNT)-conjugated CpG complex (CNT-CpG), which displayed a significant antitumor effect in gliomas. However, whether CNT-CpG could limit colon tumor growth and suppress the colon cancer liver metastasis has not been evaluated. In this study, we report CNT enhances CpG uptake in mouse colon cancer cells. Results demonstrated only CpG with CNT conjugation showed significant activation of NF-κB signal. Moreover, intratumorally delivery of CNT-CpG successfully suppressed local xenograft tumor growth and liver metastasis. CNT-CpG treatments cured 75% of mice and inhibited local tumor growth, significantly prolonged survival outcomes and limited liver metastatic tumor nodules from colon cancer cells. Using human colon cancer cell line, HCT116, we observed significantly inhibitory effects of CNT-CpG on cell growth, invasion and migration. Importantly, CNT-CpG treatment blocked the epithelial to mesenchymal transition (EMT). We compared the mRNA levels of EMT markers of colon cancer cells without or with CNT-CpG treatment from in-vitro and in-vivo models. Consistent results demonstrated expression of epithelial marker, E-cadherin was upregulated by CNT-CpG. In contrast, three mesenchymal markers, snail, fibronectin and vimentin were significantly suppressed by CNT-CpG treatment compared with control or free CpG. In summary, our data suggest CNT-CpG is an effective therapeutic approach against local colon tumor and their liver metastasis. This study presents the CNT-CpG complex as a promising therapeutic target for developing novel therapies against both local colon tumors and liver metastatic tumors. Lippincott Williams & Wilkins 2020-09-25 2021-03 /pmc/articles/PMC7861496/ /pubmed/32976213 http://dx.doi.org/10.1097/CAD.0000000000001000 Text en Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/) (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
spellingShingle | Preclinical Reports Jin, Hongyong Gao, Sujie Song, Defeng Liu, Yiting Chen, Xuebo Intratumorally CpG immunotherapy with carbon nanotubes inhibits local tumor growth and liver metastasis by suppressing the epithelial–mesenchymal transition of colon cancer cells |
title | Intratumorally CpG immunotherapy with carbon nanotubes inhibits local tumor growth and liver metastasis by suppressing the epithelial–mesenchymal transition of colon cancer cells |
title_full | Intratumorally CpG immunotherapy with carbon nanotubes inhibits local tumor growth and liver metastasis by suppressing the epithelial–mesenchymal transition of colon cancer cells |
title_fullStr | Intratumorally CpG immunotherapy with carbon nanotubes inhibits local tumor growth and liver metastasis by suppressing the epithelial–mesenchymal transition of colon cancer cells |
title_full_unstemmed | Intratumorally CpG immunotherapy with carbon nanotubes inhibits local tumor growth and liver metastasis by suppressing the epithelial–mesenchymal transition of colon cancer cells |
title_short | Intratumorally CpG immunotherapy with carbon nanotubes inhibits local tumor growth and liver metastasis by suppressing the epithelial–mesenchymal transition of colon cancer cells |
title_sort | intratumorally cpg immunotherapy with carbon nanotubes inhibits local tumor growth and liver metastasis by suppressing the epithelial–mesenchymal transition of colon cancer cells |
topic | Preclinical Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861496/ https://www.ncbi.nlm.nih.gov/pubmed/32976213 http://dx.doi.org/10.1097/CAD.0000000000001000 |
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