Stimulation of hypothalamic oxytocin neurons suppresses colorectal cancer progression in mice
- Huazhong University of Science and Technology, China
- Chinese Academy of Medical Sciences and Peking Union Medical College, China
- Tongji Medical College, Huazhong University of Science and Technology, China
Abstract
Emerging evidence suggests that the nervous system is involved in tumor development in the periphery, however, the role of 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, eg. celastrol, might be a novel strategy for colorectal cancer treatment.
Data availability
All data that support the findings of this study are included in this published article and its supplementary files. Source data files have been provided for Figures 1-7.
Article and author information
Author details
Funding
National Natural Science Foundation of China (81573146)
- Guo Zhang
National Natural Science Foundation of China (91539125)
- Guo Zhang
National Natural Science Foundation of China (81972767)
- Mei Liu
National Natural Science Foundation of China (31871089)
- Yunyun Han
National Natural Science Foundation of China (31871028)
- Man Jiang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animal procedures were approved by the IACUC at Huazhong University of Science and Technology (#2511).
Copyright
© 2021, Pan et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 625
- downloads
-
- 28
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Citations by DOI
-
- 28
- citations for umbrella DOI https://doi.org/10.7554/eLife.67535
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Stimulation of hypothalamic oxytocin neurons suppresses colorectal cancer progression in mice
eLife 10:e67535.
https://doi.org/10.7554/eLife.67535
