Abdominal ultrasound attenuates early-stage aberrant proliferation and depressive behavior in AOM/DSS-induced colorectal cancer: regulatory mechanisms of the Wnt/β-catenin pathway and HPA axis.

Chronic inflammation is a key factor promoting colorectal cancer (CRC) development and progression. Abdominal ultrasound stimulation (AUS) has shown potential in alleviating inflammatory reactions and behavioral impairments in dextran sodium sulfate (DSS)-induced colitis models by modulating the gut microbiota composition and mitigating damage to colonic tissues. This study observed the protective effects of AUS on colitis and mice with early-stage CRC and clarified the mechanism potentially underlying these effects. CRC was induced in mice using azoxymethane (AOM)/DSS. Low-intensity pulsed ultrasound (LIPUS) was then applied to the abdominal region of mice at intensities of 0.5 and 1.0 W/cm2. Therapeutic effects were evaluated using the disease activity index (DAI), histopathological analysis, endoscopic assessment, and behavioral tests. RNA sequencing was performed to profile colonic transcriptomic changes and associated pathways. Abdominal LIPUS treatment significantly alleviated AOM/DSS-induced DAI elevation, colon shortening, histological damage, and intestinal tumor formation in mice. It also significantly improved CRC-associated depressive behavior. RNA-seq and pathway analysis showed that LIPUS impacted key signaling pathways, including Wnt and folate-mediated one-carbon metabolism pathways. Moreover, Wnt/β-catenin pathway downstream proteins and hypothalamic-pituitary-adrenal (HPA) axis hyperactivity were significantly downregulated in AOM/DSS-treated mice after LIPUS treatment. Abdominal LIPUS appears to have a dual therapeutic effect, attenuation of tumor burden and depressive phenotypes, through the modulation of systemic inflammation and correction of HPA axis dysregulation in the AOM/DSS-induced CRC model. These insights support the potential of AUS as a non-invasive physical modality for CRC prevention or therapy, which warrants further investigation.