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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...

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Autores principales: Pan, Susu, Yin, Kaili, Tang, Zhiwei, Wang, Shuren, Chen, Zhuo, Wang, Yirong, Zhu, Hongxia, Han, Yunyun, Liu, Mei, Jiang, Man, Xu, Ningzhi, Zhang, Guo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
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.
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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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