Cargando…
Fasting mimicking diet inhibits tumor-associated macrophage survival and pro-tumor function in hypoxia: implications for combination therapy with anti-angiogenic agent
BACKGROUND: Recent research shows that tumor-associated macrophages (TAMs) are the primary consumers of glucose in tumor tissue, surpassing that of tumor cells. Our previous studies revealed that inhibiting glucose uptake impairs the survival and tumor-promoting function of hypoxic TAMs, suggesting...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10601181/ https://www.ncbi.nlm.nih.gov/pubmed/37884960 http://dx.doi.org/10.1186/s12967-023-04577-7 |
_version_ | 1785126143070830592 |
---|---|
author | Wang, Lei Wang, Yu-jie Wang, Rong Gong, Fu-lian Shi, Yu-huan Li, Sheng-nan Chen, Pan-pan Yuan, Yong-fang |
author_facet | Wang, Lei Wang, Yu-jie Wang, Rong Gong, Fu-lian Shi, Yu-huan Li, Sheng-nan Chen, Pan-pan Yuan, Yong-fang |
author_sort | Wang, Lei |
collection | PubMed |
description | BACKGROUND: Recent research shows that tumor-associated macrophages (TAMs) are the primary consumers of glucose in tumor tissue, surpassing that of tumor cells. Our previous studies revealed that inhibiting glucose uptake impairs the survival and tumor-promoting function of hypoxic TAMs, suggesting that glucose reduction by energy restriction (calorie restriction or short-term fasting) may has a significant impact on TAMs. The purpose of this study is to verify the effect of fasting-mimicking diet (FMD) on TAMs, and to determine whether FMD synergizes with anti-angiogenic drug apatinib via TAMs. METHODS: The effect of FMD on TAMs and its synergistic effects with apatinib were observed using an orthotopic mouse breast cancer model. An in vitro cell model, utilizing M2 macrophages derived from THP-1 cell line, was intended to assess the effects of low glucose on TAMs under hypoxic and normoxic conditions. Bioinformatics was used to screen for potential mechanisms of action, which were then validated both in vivo and in vitro. RESULTS: FMD significantly inhibit the pro-tumor function of TAMs in vivo and in vitro, with the inhibitory effect being more pronounced under hypoxic conditions. Additionally, the combination of FMD-mediated TAMs inhibition with apatinib results in synergistic anti-tumor activity. This effect is partially mediated by the downregulation of CCL8 expression and secretion by the mTOR-HIF-1α signaling pathway. CONCLUSIONS: These results support further clinical combination studies of FMD and anti-angiogenic therapy as potential anti-tumor strategies. GRAPHICAL ABSTRACT: [Image: see text] |
format | Online Article Text |
id | pubmed-10601181 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-106011812023-10-27 Fasting mimicking diet inhibits tumor-associated macrophage survival and pro-tumor function in hypoxia: implications for combination therapy with anti-angiogenic agent Wang, Lei Wang, Yu-jie Wang, Rong Gong, Fu-lian Shi, Yu-huan Li, Sheng-nan Chen, Pan-pan Yuan, Yong-fang J Transl Med Research BACKGROUND: Recent research shows that tumor-associated macrophages (TAMs) are the primary consumers of glucose in tumor tissue, surpassing that of tumor cells. Our previous studies revealed that inhibiting glucose uptake impairs the survival and tumor-promoting function of hypoxic TAMs, suggesting that glucose reduction by energy restriction (calorie restriction or short-term fasting) may has a significant impact on TAMs. The purpose of this study is to verify the effect of fasting-mimicking diet (FMD) on TAMs, and to determine whether FMD synergizes with anti-angiogenic drug apatinib via TAMs. METHODS: The effect of FMD on TAMs and its synergistic effects with apatinib were observed using an orthotopic mouse breast cancer model. An in vitro cell model, utilizing M2 macrophages derived from THP-1 cell line, was intended to assess the effects of low glucose on TAMs under hypoxic and normoxic conditions. Bioinformatics was used to screen for potential mechanisms of action, which were then validated both in vivo and in vitro. RESULTS: FMD significantly inhibit the pro-tumor function of TAMs in vivo and in vitro, with the inhibitory effect being more pronounced under hypoxic conditions. Additionally, the combination of FMD-mediated TAMs inhibition with apatinib results in synergistic anti-tumor activity. This effect is partially mediated by the downregulation of CCL8 expression and secretion by the mTOR-HIF-1α signaling pathway. CONCLUSIONS: These results support further clinical combination studies of FMD and anti-angiogenic therapy as potential anti-tumor strategies. GRAPHICAL ABSTRACT: [Image: see text] BioMed Central 2023-10-26 /pmc/articles/PMC10601181/ /pubmed/37884960 http://dx.doi.org/10.1186/s12967-023-04577-7 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Wang, Lei Wang, Yu-jie Wang, Rong Gong, Fu-lian Shi, Yu-huan Li, Sheng-nan Chen, Pan-pan Yuan, Yong-fang Fasting mimicking diet inhibits tumor-associated macrophage survival and pro-tumor function in hypoxia: implications for combination therapy with anti-angiogenic agent |
title | Fasting mimicking diet inhibits tumor-associated macrophage survival and pro-tumor function in hypoxia: implications for combination therapy with anti-angiogenic agent |
title_full | Fasting mimicking diet inhibits tumor-associated macrophage survival and pro-tumor function in hypoxia: implications for combination therapy with anti-angiogenic agent |
title_fullStr | Fasting mimicking diet inhibits tumor-associated macrophage survival and pro-tumor function in hypoxia: implications for combination therapy with anti-angiogenic agent |
title_full_unstemmed | Fasting mimicking diet inhibits tumor-associated macrophage survival and pro-tumor function in hypoxia: implications for combination therapy with anti-angiogenic agent |
title_short | Fasting mimicking diet inhibits tumor-associated macrophage survival and pro-tumor function in hypoxia: implications for combination therapy with anti-angiogenic agent |
title_sort | fasting mimicking diet inhibits tumor-associated macrophage survival and pro-tumor function in hypoxia: implications for combination therapy with anti-angiogenic agent |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10601181/ https://www.ncbi.nlm.nih.gov/pubmed/37884960 http://dx.doi.org/10.1186/s12967-023-04577-7 |
work_keys_str_mv | AT wanglei fastingmimickingdietinhibitstumorassociatedmacrophagesurvivalandprotumorfunctioninhypoxiaimplicationsforcombinationtherapywithantiangiogenicagent AT wangyujie fastingmimickingdietinhibitstumorassociatedmacrophagesurvivalandprotumorfunctioninhypoxiaimplicationsforcombinationtherapywithantiangiogenicagent AT wangrong fastingmimickingdietinhibitstumorassociatedmacrophagesurvivalandprotumorfunctioninhypoxiaimplicationsforcombinationtherapywithantiangiogenicagent AT gongfulian fastingmimickingdietinhibitstumorassociatedmacrophagesurvivalandprotumorfunctioninhypoxiaimplicationsforcombinationtherapywithantiangiogenicagent AT shiyuhuan fastingmimickingdietinhibitstumorassociatedmacrophagesurvivalandprotumorfunctioninhypoxiaimplicationsforcombinationtherapywithantiangiogenicagent AT lishengnan fastingmimickingdietinhibitstumorassociatedmacrophagesurvivalandprotumorfunctioninhypoxiaimplicationsforcombinationtherapywithantiangiogenicagent AT chenpanpan fastingmimickingdietinhibitstumorassociatedmacrophagesurvivalandprotumorfunctioninhypoxiaimplicationsforcombinationtherapywithantiangiogenicagent AT yuanyongfang fastingmimickingdietinhibitstumorassociatedmacrophagesurvivalandprotumorfunctioninhypoxiaimplicationsforcombinationtherapywithantiangiogenicagent |