The risk factors for colorectal cancer liver metastasis in a mouse model of Alzheimer's disease

Abstract

Background and Objective: To investigate the occurrence of colorectal cancer (CRC) liver metastasis (CRLM) and the risk factors in mice with Alzheimer's disease (AD). methods: Mice in the AD group (APP/PS1 models of AD) and the control (CON) group (wild-type C57BL/6J mice) were injected with MC38 cells to establish CRLM models. After the experiment, the tumor nodules on liver surface were counted, and the liver weight, volume were measured. 16S rDNA sequencing, enzyme-linked immunosorbent assay, Pearson’s analysis and immunohistochemical technique were showed to investigate the impact of AD on CRLM and its possible mechanism. Results: Compared to the CON group, the AD group exhibited a increase in the number of tumor nodules on the liver surface, with consistent findings in both liver weight and volume measurements correlating with the metastatic count. Analysis of 16S rDNA sequencing revealed distinct alterations in the intestinal microbiota of the AD group. Furthermore, relative to the CON group, the AD group exhibited notably elevated levels of NGF expression in both the colon and liver. Additionally, discernibly elevated concentrations of VEGF and CXCL12 were observed in both serum and liver tissues of the AD group compared to the CON group. The results of Pearson correlation analysis indicated positive correlations between intestinal NGF levels and both hepatic CXCL12 and VEGF levels. The AD group had smaller number of hepatic KCs than that in the CON group. Conclusions: AD accelerates CRLM. The mechanism may be caused by gut flora affecting hepatic KCs, thus linking the brain-gut-liver axis.