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Rapamycin Liposomes Combined with 5-Fluorouracil Inhibits Angiogenesis and Tumor Growth of APC ((Min/+)) Mice and AOM/DSS-Induced Colorectal Cancer Mice
BACKGROUND: Transgenic C57BL/6-APC((Min/+)) spontaneous cancer mouse model and the Azoxymethane (AOM)/Dextran Sulfate Sodium (DSS) chemically induced orthotopic colorectal cancer mouse model represented distinct pathogenesis of colorectal cancers. Our previous study revealed that the combination of...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Dove
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9621024/ https://www.ncbi.nlm.nih.gov/pubmed/36325149 http://dx.doi.org/10.2147/IJN.S373777 |
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author | Liu, Xiao-Min Zhu, Wen-Ting Jia, Meng-Lei Li, Yu-Ting Hong, Ye Liu, Zhong-Qiu Yan, Peng-Ke |
author_facet | Liu, Xiao-Min Zhu, Wen-Ting Jia, Meng-Lei Li, Yu-Ting Hong, Ye Liu, Zhong-Qiu Yan, Peng-Ke |
author_sort | Liu, Xiao-Min |
collection | PubMed |
description | BACKGROUND: Transgenic C57BL/6-APC((Min/+)) spontaneous cancer mouse model and the Azoxymethane (AOM)/Dextran Sulfate Sodium (DSS) chemically induced orthotopic colorectal cancer mouse model represented distinct pathogenesis of colorectal cancers. Our previous study revealed that the combination of Rapamycin liposomes (Rapa/Lps) and 5-Fluorouracil (5-FU) has anti-colorectal cancer effects. However, the therapeutic efficacy of Rapa/Lps and 5-FU in other colorectal cancer mice models is yet to be thoroughly explored. The purpose of this study was to investigate the anti-tumor effect of Rapa/Lps combined with 5-FU in vivo and in vitro. METHODS: In this study, we evaluated the effect of Rapa/Lps and 5-FU on APC ((Min/+)) mice and AOM/DSS-induced colorectal cancer mice. The small intestine, colorectum, serum, and plasma of mice in each group were collected following sacrifice to record the number of tumors. HE staining was utilized for observing pathological damage to intestine tissues. Tube formation assay, Transwell assay, wound healing assay, Western Blot were used to explore the anti-angiogenesis effect of drugs in HUVECs. RESULTS: As expected, Rapa/Lps and 5-FU significantly suppressed tumor formation, decreased the number of tumors, and tumor load both in two mouse models, and had no influence on mouse weight. Mechanically, the anti-tumor effect of the drug also was associated in inhibiting angiogenesis and proliferation. Furthermore, we found that Rapa/Lps obviously inhibited HUVECs tube formation and migration. CONCLUSION: Altogether, we revealed the Rapa/Lps synergism with 5-FU decreased colon and small intestinal tumorigenesis in AOM/DSS-treated and APC ((Min/+)) mice, respectively, and correlated with anti-angiogenesis. |
format | Online Article Text |
id | pubmed-9621024 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-96210242022-11-01 Rapamycin Liposomes Combined with 5-Fluorouracil Inhibits Angiogenesis and Tumor Growth of APC ((Min/+)) Mice and AOM/DSS-Induced Colorectal Cancer Mice Liu, Xiao-Min Zhu, Wen-Ting Jia, Meng-Lei Li, Yu-Ting Hong, Ye Liu, Zhong-Qiu Yan, Peng-Ke Int J Nanomedicine Original Research BACKGROUND: Transgenic C57BL/6-APC((Min/+)) spontaneous cancer mouse model and the Azoxymethane (AOM)/Dextran Sulfate Sodium (DSS) chemically induced orthotopic colorectal cancer mouse model represented distinct pathogenesis of colorectal cancers. Our previous study revealed that the combination of Rapamycin liposomes (Rapa/Lps) and 5-Fluorouracil (5-FU) has anti-colorectal cancer effects. However, the therapeutic efficacy of Rapa/Lps and 5-FU in other colorectal cancer mice models is yet to be thoroughly explored. The purpose of this study was to investigate the anti-tumor effect of Rapa/Lps combined with 5-FU in vivo and in vitro. METHODS: In this study, we evaluated the effect of Rapa/Lps and 5-FU on APC ((Min/+)) mice and AOM/DSS-induced colorectal cancer mice. The small intestine, colorectum, serum, and plasma of mice in each group were collected following sacrifice to record the number of tumors. HE staining was utilized for observing pathological damage to intestine tissues. Tube formation assay, Transwell assay, wound healing assay, Western Blot were used to explore the anti-angiogenesis effect of drugs in HUVECs. RESULTS: As expected, Rapa/Lps and 5-FU significantly suppressed tumor formation, decreased the number of tumors, and tumor load both in two mouse models, and had no influence on mouse weight. Mechanically, the anti-tumor effect of the drug also was associated in inhibiting angiogenesis and proliferation. Furthermore, we found that Rapa/Lps obviously inhibited HUVECs tube formation and migration. CONCLUSION: Altogether, we revealed the Rapa/Lps synergism with 5-FU decreased colon and small intestinal tumorigenesis in AOM/DSS-treated and APC ((Min/+)) mice, respectively, and correlated with anti-angiogenesis. Dove 2022-10-27 /pmc/articles/PMC9621024/ /pubmed/36325149 http://dx.doi.org/10.2147/IJN.S373777 Text en © 2022 Liu et al. https://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/ (https://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 Liu, Xiao-Min Zhu, Wen-Ting Jia, Meng-Lei Li, Yu-Ting Hong, Ye Liu, Zhong-Qiu Yan, Peng-Ke Rapamycin Liposomes Combined with 5-Fluorouracil Inhibits Angiogenesis and Tumor Growth of APC ((Min/+)) Mice and AOM/DSS-Induced Colorectal Cancer Mice |
title | Rapamycin Liposomes Combined with 5-Fluorouracil Inhibits Angiogenesis and Tumor Growth of APC ((Min/+)) Mice and AOM/DSS-Induced Colorectal Cancer Mice |
title_full | Rapamycin Liposomes Combined with 5-Fluorouracil Inhibits Angiogenesis and Tumor Growth of APC ((Min/+)) Mice and AOM/DSS-Induced Colorectal Cancer Mice |
title_fullStr | Rapamycin Liposomes Combined with 5-Fluorouracil Inhibits Angiogenesis and Tumor Growth of APC ((Min/+)) Mice and AOM/DSS-Induced Colorectal Cancer Mice |
title_full_unstemmed | Rapamycin Liposomes Combined with 5-Fluorouracil Inhibits Angiogenesis and Tumor Growth of APC ((Min/+)) Mice and AOM/DSS-Induced Colorectal Cancer Mice |
title_short | Rapamycin Liposomes Combined with 5-Fluorouracil Inhibits Angiogenesis and Tumor Growth of APC ((Min/+)) Mice and AOM/DSS-Induced Colorectal Cancer Mice |
title_sort | rapamycin liposomes combined with 5-fluorouracil inhibits angiogenesis and tumor growth of apc ((min/+)) mice and aom/dss-induced colorectal cancer mice |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9621024/ https://www.ncbi.nlm.nih.gov/pubmed/36325149 http://dx.doi.org/10.2147/IJN.S373777 |
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