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Borneol and Tetrandrine Modulate the Blood–Brain Barrier and Blood–Tumor Barrier to Improve the Therapeutic Efficacy of 5-Fluorouracil in Brain Metastasis
The efficacy of chemotherapeutic drugs for the treatment of brain metastasis may be compromised by the blood–brain barrier (BBB) and blood–tumor barrier (BTB). P-glycoprotein (P-gp) is a multidrug resistance protein that potentially limits the penetration of chemotherapeutics through the BBB and BTB...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8855435/ https://www.ncbi.nlm.nih.gov/pubmed/35168384 http://dx.doi.org/10.1177/15347354221077682 |
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author | Lin, Jui-Feng Liu, Yen-Shuo Huang, Yu-Chuen Chi, Chih-Wen Tsai, Cheng-Chia Tsai, Tung-Hu Chen, Yu-Jen |
author_facet | Lin, Jui-Feng Liu, Yen-Shuo Huang, Yu-Chuen Chi, Chih-Wen Tsai, Cheng-Chia Tsai, Tung-Hu Chen, Yu-Jen |
author_sort | Lin, Jui-Feng |
collection | PubMed |
description | The efficacy of chemotherapeutic drugs for the treatment of brain metastasis may be compromised by the blood–brain barrier (BBB) and blood–tumor barrier (BTB). P-glycoprotein (P-gp) is a multidrug resistance protein that potentially limits the penetration of chemotherapeutics through the BBB and BTB. 5-Fluorouracil (5-FU) is widely used to treat cancer. Bioactive constituents of medicinal herbs, such as borneol and tetrandrine, potentially improve drug penetration through the BBB and BTB. We hypothesized that borneol and tetrandrine might modulate the BBB and BTB to enhance 5-FU penetration into the brain. To investigate this, in vitro and in vivo models were developed to explore the modulatory effects of borneol and tetrandrine on 5-FU penetration through the BBB and BTB. In the in vitro models, barrier integrity, cell viability, barrier penetration, P-gp activity, and NF-κB expression were assessed. In the in vivo brain metastasis models, cancer cells were injected into the internal carotid artery to evaluate tumor growth. The experimental results demonstrated that borneol and borneol + tetrandrine reduced BBB integrity. The efflux pump function of P-gp was partially inhibited by tetrandrine and borneol + tetrandrine. In the in vivo experiment, borneol + tetrandrine effectively prolonged survival without compromising body weight. In conclusion, BBB and BTB integrity was modulated by borneol and borneol + tetrandrine. The combination of borneol and tetrandrine could be used to improve the chemotherapeutic control of brain metastasis. |
format | Online Article Text |
id | pubmed-8855435 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-88554352022-02-19 Borneol and Tetrandrine Modulate the Blood–Brain Barrier and Blood–Tumor Barrier to Improve the Therapeutic Efficacy of 5-Fluorouracil in Brain Metastasis Lin, Jui-Feng Liu, Yen-Shuo Huang, Yu-Chuen Chi, Chih-Wen Tsai, Cheng-Chia Tsai, Tung-Hu Chen, Yu-Jen Integr Cancer Ther Research Article The efficacy of chemotherapeutic drugs for the treatment of brain metastasis may be compromised by the blood–brain barrier (BBB) and blood–tumor barrier (BTB). P-glycoprotein (P-gp) is a multidrug resistance protein that potentially limits the penetration of chemotherapeutics through the BBB and BTB. 5-Fluorouracil (5-FU) is widely used to treat cancer. Bioactive constituents of medicinal herbs, such as borneol and tetrandrine, potentially improve drug penetration through the BBB and BTB. We hypothesized that borneol and tetrandrine might modulate the BBB and BTB to enhance 5-FU penetration into the brain. To investigate this, in vitro and in vivo models were developed to explore the modulatory effects of borneol and tetrandrine on 5-FU penetration through the BBB and BTB. In the in vitro models, barrier integrity, cell viability, barrier penetration, P-gp activity, and NF-κB expression were assessed. In the in vivo brain metastasis models, cancer cells were injected into the internal carotid artery to evaluate tumor growth. The experimental results demonstrated that borneol and borneol + tetrandrine reduced BBB integrity. The efflux pump function of P-gp was partially inhibited by tetrandrine and borneol + tetrandrine. In the in vivo experiment, borneol + tetrandrine effectively prolonged survival without compromising body weight. In conclusion, BBB and BTB integrity was modulated by borneol and borneol + tetrandrine. The combination of borneol and tetrandrine could be used to improve the chemotherapeutic control of brain metastasis. SAGE Publications 2022-02-16 /pmc/articles/PMC8855435/ /pubmed/35168384 http://dx.doi.org/10.1177/15347354221077682 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Research Article Lin, Jui-Feng Liu, Yen-Shuo Huang, Yu-Chuen Chi, Chih-Wen Tsai, Cheng-Chia Tsai, Tung-Hu Chen, Yu-Jen Borneol and Tetrandrine Modulate the Blood–Brain Barrier and Blood–Tumor Barrier to Improve the Therapeutic Efficacy of 5-Fluorouracil in Brain Metastasis |
title | Borneol and Tetrandrine Modulate the Blood–Brain Barrier and
Blood–Tumor Barrier to Improve the Therapeutic Efficacy of 5-Fluorouracil in
Brain Metastasis |
title_full | Borneol and Tetrandrine Modulate the Blood–Brain Barrier and
Blood–Tumor Barrier to Improve the Therapeutic Efficacy of 5-Fluorouracil in
Brain Metastasis |
title_fullStr | Borneol and Tetrandrine Modulate the Blood–Brain Barrier and
Blood–Tumor Barrier to Improve the Therapeutic Efficacy of 5-Fluorouracil in
Brain Metastasis |
title_full_unstemmed | Borneol and Tetrandrine Modulate the Blood–Brain Barrier and
Blood–Tumor Barrier to Improve the Therapeutic Efficacy of 5-Fluorouracil in
Brain Metastasis |
title_short | Borneol and Tetrandrine Modulate the Blood–Brain Barrier and
Blood–Tumor Barrier to Improve the Therapeutic Efficacy of 5-Fluorouracil in
Brain Metastasis |
title_sort | borneol and tetrandrine modulate the blood–brain barrier and
blood–tumor barrier to improve the therapeutic efficacy of 5-fluorouracil in
brain metastasis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8855435/ https://www.ncbi.nlm.nih.gov/pubmed/35168384 http://dx.doi.org/10.1177/15347354221077682 |
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