Lunasin‑Rich Soybean Extract Attenuates MMP‑9 Expression in an AOM/DSS Mouse Model of Colitis‑Associated Colorectal Cancer

Abstract

Background: Colorectal cancer (CRC) ranks as the third most common malignancy globally and is strongly associated with chronic inflammation, particularly colitis-associated cancer (CAC). Matrix metalloproteinase-9 (MMP-9) is a key enzyme in tumor invasion, angiogenesis, and metastasis. Lunasin, a 44–amino acid peptide derived from soybeans, exhibits anti-inflammatory and anticancer activities, but its role in modulating MMP-9 in CAC remains unclear.

Methods: Thirty male Swiss Webster mice (12 weeks, ~25 g) were randomly assigned to six groups: normal control, negative control, positive control, and three lunasin-rich soybean extract (LRSE) groups (250, 300, 350 mg/kg). CAC was induced using a single intraperitoneal injection of azoxymethane (10 mg/kg) followed by 2% dextran sodium sulfate in drinking water for 7 days. Treatments were given orally for 4 weeks. Colon tissues were collected, and MMP-9 expression was assessed by immunohistochemistry and quantified using the H-score. Data were analyzed with Welch’s ANOVA and Games–Howell post hoc test.

Results: Azoxymethane/Dextran sodium sulfate (AOM/DSS) significantly increased MMP-9 expression compared with normal controls (p < 0.001). Aspirin reduced MMP-9 expression relative to the negative control (p = 0.001). LRSE significantly decreased MMP-9 expression at doses of 250 mg/kg (p = 0.048) and 350 mg/kg (p = 0.001), while the 300 mg/kg dose showed no significant effect. The inhibitory effect of LRSE did not display a clear dose–response pattern.

Conclusion: LRSE significantly reduced MMP-9 expression in an AOM/DSS-induced CAC mouse model, supporting its potential as a natural chemopreventive agent. Further research with larger cohorts and molecular pathway analyses is warranted.