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Stimulation of hypothalamic oxytocin neurons suppresses colorectal cancer progression in mice
Emerging evidence suggests that the nervous system is involved in tumor development in the periphery, however, the role of the central nervous system remains largely unknown. Here, by combining genetic, chemogenetic, pharmacological, and electrophysiological approaches, we show that hypothalamic oxy...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8536257/ https://www.ncbi.nlm.nih.gov/pubmed/34528509 http://dx.doi.org/10.7554/eLife.67535 |
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author | Pan, Susu Yin, Kaili Tang, Zhiwei Wang, Shuren Chen, Zhuo Wang, Yirong Zhu, Hongxia Han, Yunyun Liu, Mei Jiang, Man Xu, Ningzhi Zhang, Guo |
author_facet | Pan, Susu Yin, Kaili Tang, Zhiwei Wang, Shuren Chen, Zhuo Wang, Yirong Zhu, Hongxia Han, Yunyun Liu, Mei Jiang, Man Xu, Ningzhi Zhang, Guo |
author_sort | Pan, Susu |
collection | PubMed |
description | Emerging evidence suggests that the nervous system is involved in tumor development in the periphery, however, the role of the central nervous system remains largely unknown. Here, by combining genetic, chemogenetic, pharmacological, and electrophysiological approaches, we show that hypothalamic oxytocin (Oxt)-producing neurons modulate colitis-associated cancer (CAC) progression in mice. Depletion or activation of Oxt neurons could augment or suppress CAC progression. Importantly, brain treatment with celastrol, a pentacyclic triterpenoid, excites Oxt neurons and inhibits CAC progression, and this anti-tumor effect was significantly attenuated in Oxt neuron-lesioned mice. Furthermore, brain treatment with celastrol suppresses sympathetic neuronal activity in the celiac-superior mesenteric ganglion (CG-SMG), and activation of β2 adrenergic receptor abolishes the anti-tumor effect of Oxt neuron activation or centrally administered celastrol. Taken together, these findings demonstrate that hypothalamic Oxt neurons regulate CAC progression by modulating the neuronal activity in the CG-SMG. Stimulation of Oxt neurons using chemicals, for example, celastrol, might be a novel strategy for colorectal cancer treatment. |
format | Online Article Text |
id | pubmed-8536257 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-85362572021-10-25 Stimulation of hypothalamic oxytocin neurons suppresses colorectal cancer progression in mice Pan, Susu Yin, Kaili Tang, Zhiwei Wang, Shuren Chen, Zhuo Wang, Yirong Zhu, Hongxia Han, Yunyun Liu, Mei Jiang, Man Xu, Ningzhi Zhang, Guo eLife Cancer Biology Emerging evidence suggests that the nervous system is involved in tumor development in the periphery, however, the role of the central nervous system remains largely unknown. Here, by combining genetic, chemogenetic, pharmacological, and electrophysiological approaches, we show that hypothalamic oxytocin (Oxt)-producing neurons modulate colitis-associated cancer (CAC) progression in mice. Depletion or activation of Oxt neurons could augment or suppress CAC progression. Importantly, brain treatment with celastrol, a pentacyclic triterpenoid, excites Oxt neurons and inhibits CAC progression, and this anti-tumor effect was significantly attenuated in Oxt neuron-lesioned mice. Furthermore, brain treatment with celastrol suppresses sympathetic neuronal activity in the celiac-superior mesenteric ganglion (CG-SMG), and activation of β2 adrenergic receptor abolishes the anti-tumor effect of Oxt neuron activation or centrally administered celastrol. Taken together, these findings demonstrate that hypothalamic Oxt neurons regulate CAC progression by modulating the neuronal activity in the CG-SMG. Stimulation of Oxt neurons using chemicals, for example, celastrol, might be a novel strategy for colorectal cancer treatment. eLife Sciences Publications, Ltd 2021-09-16 /pmc/articles/PMC8536257/ /pubmed/34528509 http://dx.doi.org/10.7554/eLife.67535 Text en © 2021, Pan et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Cancer Biology Pan, Susu Yin, Kaili Tang, Zhiwei Wang, Shuren Chen, Zhuo Wang, Yirong Zhu, Hongxia Han, Yunyun Liu, Mei Jiang, Man Xu, Ningzhi Zhang, Guo Stimulation of hypothalamic oxytocin neurons suppresses colorectal cancer progression in mice |
title | Stimulation of hypothalamic oxytocin neurons suppresses colorectal cancer progression in mice |
title_full | Stimulation of hypothalamic oxytocin neurons suppresses colorectal cancer progression in mice |
title_fullStr | Stimulation of hypothalamic oxytocin neurons suppresses colorectal cancer progression in mice |
title_full_unstemmed | Stimulation of hypothalamic oxytocin neurons suppresses colorectal cancer progression in mice |
title_short | Stimulation of hypothalamic oxytocin neurons suppresses colorectal cancer progression in mice |
title_sort | stimulation of hypothalamic oxytocin neurons suppresses colorectal cancer progression in mice |
topic | Cancer Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8536257/ https://www.ncbi.nlm.nih.gov/pubmed/34528509 http://dx.doi.org/10.7554/eLife.67535 |
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