Hwang Soonjae, Lee Yeram, Rhee Ki-Jong
Department of Biochemistry, Lee Gil Ya Cancer and Diabetes Institute, College of Medicine, Gachon University, 155 Gaetbeol-ro, Yeonsu-gu, Incheon 21999, Republic of Korea.
Department of Health Sciences and Technology, GAIHST (Gachon Advanced Institute for Health Sciences & Technology), Gachon University, Incheon 21999, Republic of Korea.
Int J Mol Sci. 2025 Jun 27;26(13):6218. doi: 10.3390/ijms26136218.
Enterotoxigenic (ETBF) promotes colitis-associated cancer through the toxin (BFT), which induces colonic inflammation that can be exacerbated by external stimuli. We found that BALB/c mice infected with ETBF and treated with azoxymethane and dextran sodium sulfate (DSS) developed numerous distal colon polyps more rapidly than B6 mice, suggesting strain differences in ETBF-induced tumorigenicity. Using a gene-deficient ETBF strain, we confirmed BFT's crucial role in ETBF-promoted tumorigenesis and inflammation. While both 1% and 2% DSS induced comparable polyp formation, 1% DSS minimized mortality, proving sufficient for maximizing polyp development. Mechanistically, BFT-mediated tumorigenesis involves NF-κB/CXCL1 signaling in colonic epithelial cells exposed to BFT and DSS, a pathway known to be critical for inflammation and cancer progression. This model provides a valuable platform for dissecting ETBF's colitis-associated cancer-promoting mechanisms, particularly those involving BFT, and for evaluating BFT-targeted therapeutic interventions.
产肠毒素脆弱拟杆菌（ETBF）通过毒素（BFT）促进结肠炎相关癌症，该毒素会引发结肠炎症，外部刺激可使其加剧。我们发现，感染ETBF并接受氧化偶氮甲烷和葡聚糖硫酸钠（DSS）处理的BALB/c小鼠比B6小鼠更快地长出大量远端结肠息肉，这表明ETBF诱导的致瘤性存在品系差异。使用基因缺陷型ETBF菌株，我们证实了BFT在ETBF促进的肿瘤发生和炎症中起关键作用。虽然1%和2%的DSS诱导的息肉形成相当，但1%的DSS将死亡率降至最低，证明足以使息肉发育最大化。从机制上讲，BFT介导的肿瘤发生涉及暴露于BFT和DSS的结肠上皮细胞中的NF-κB/CXCL1信号传导，该途径已知对炎症和癌症进展至关重要。该模型为剖析ETBF的结肠炎相关癌症促进机制，特别是涉及BFT的机制，以及评估针对BFT的治疗干预措施提供了一个有价值的平台。
