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.
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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.
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Stimulation of hypothalamic oxytocin neurons suppresses colorectal cancer progression in mice
eLife 10:e67535.
https://doi.org/10.7554/eLife.67535
