Protective Role of the Hepatic Vagus Nerve against Liver Metastasis in Mice

Objective(s): Although accumulating evidence has shown that the autonomic nervous system is involved in liver pathology, its role in regulating cancer development remains unclear. The purpose of this study was to elucidate its detailed mechanisms. Methods: A mouse model of liver metastasis of colorectal cancer was used. To elucidate the potential mechanisms involved, we examined the effect of selective hepatic vagotomy on the survival rate and liver-to-body weight. We further evaluated the possible involvement of the hepatic sympathetic nerve fibers in this model. Results: The mortality rate and the liver-to-body weight ratio after cancer inoculation were significantly higher in the vagotomized mice than in the sham-operated mice. The vagotomized mice exhibited a transient decrease in hepatic norepinephrine levels following cancer inoculation. Interestingly, the vagotomy-induced exacerbation of liver metastasis was attenuated by supplementary norepinephrine or phenylephrine, a selective α₁-adrenoceptor agonist, but not by clonidine, a selective α₂-adrenoceptor agonist. Conclusion: Collectively, these results suggest that the hepatic vagus nerve may play a protective role against liver metastasis. Hepatic sympathetic nerves may also be involved as a protective efferent loop, possibly acting through the α₁-adrenoceptor.