393 modulates KRAS and APC expression and cytokine levels in colitis-associated colon cancer.

BACKGROUND

Colitis-associated colon cancer (CAC) is a specific subset of colorectal cancer (CRC) affecting patients with inflammatory bowel diseases (IBDs). Chronic colon inflammation orchestrates immune surveillance or escape and may drive neoplastic initiation and progression. 393 ( 393) is a lactic acid microorganism that, beyond its nutritional value, provides health benefits. To explore the therapeutic potential of this probiotic against CAC, we evaluated colon histopathology, circulating cytokines, and the expression of the Kristen rat viral sarcoma oncogene homolog (KRAS) and the adenomatosis polyposis coli (APC) tumor-suppressing gene in the murine model of CAC induced with azoxymethane (AOM) and dextran sodium sulfate (DSS).

METHODS

BALB/c mice (n=7/group) received two doses of AOM (10 mg/kg body weight) followed by three 5-day cycles of 2% DSS. 393 was administered orally [1×10 colony forming units (CFU)/100 µL/mouse/twice a week/6 months] either alone, before AOM-DSS, or starting at the same time as AOM-DSS. Colon histopathology was assessed by hematoxylin-eosin staining, circulating cytokines by flow cytometry, and the expression of colonic KRAS and APC by quantitative reverse transcription polymerase chain reaction (RT-qPCR).

RESULTS

AOM-DSS induced CAC in BALB/c mice, which presented severe colon damage, high cytokine levels, and altered KRAS and APC expression. Conversely, 393 ingestions, starting at the same time as CAC induction, restored colon architecture and modulated cytokine levels and gene expression.

CONCLUSIONS

The present experimental work supports the therapeutic potential of 393 against CAC, as it shows that its ingestion restored the damaging effect of AOM-DSS through its anti-inflammatory properties that helped modulate KRAS and APC mRNA expression.