Lee Su-Mi, Park Seon-Young, Sophallika Khom, Chung Jin Ook, Jung Yong Wook, Kim Dong Hyun, Kim Jin Won, Kim Hyun Soo, Yoon Jae Hyun, Jung Young Do, Ju Jae Kyun, Chung Jun Seong, Kwak Han Deok
Department of Internal Medicine, Chonnam National University Medical School, Gwangju, South Korea.
Chonnam National University Hospital, 42 Jaebong-ro, Donggu, Gwangju, 61572, South Korea.
Sci Rep. 2025 Aug 11;15(1):29413. doi: 10.1038/s41598-025-15159-6.
Bile acid (BA) metabolism and signaling may influence cancer risk. We investigated differences in circulating BA composition between healthy controls and patients with colorectal cancer (CRC) and assessed the epithelial-mesenchymal transition (EMT) in CRC cell lines exposed to chenodeoxycholic acid (CDCA). BA, C4, and fibroblast growth factor-19 (FGF19) concentrations in serum samples from 70 controls and 133 patients with CRC were analyzed. Results showed that primary and secondary BAs, C4, and FGF19 were significantly lower in CRC patients than in the age- and sex- matched controls (P < 0.05). CDCA reduced the percentage of EdU-positive cells in HCT116 and HT-29 cells by 53.6% and 28.3%, respectively (P < 0.001) and decreased the rate of wound closure by 0.31 ± 0.05- and 0.30 ± 0.06-fold in HCT116 and HT-29 cells, respectively(P < 0.05). It significantly reduced spheroid formation by 90.0% and 94.3% in HCT116 and HT-29 cells, respectively (P < 0.0001) and downregulated EMT-related stem cell markers in CRC cells. The dysregulation of BA synthesis and recycling might contribute to CRC carcinogenesis. CDCA might alter EMT, protecting against CRC development and progression. The predictive role of plasma BAs in CRC prognosis and their potential in CRC prevention and management should be further explored.
胆汁酸（BA）代谢及信号传导可能影响癌症风险。我们研究了健康对照者与结直肠癌（CRC）患者循环胆汁酸组成的差异，并评估了暴露于鹅去氧胆酸（CDCA）的CRC细胞系中的上皮-间质转化（EMT）。分析了70名对照者和133名CRC患者血清样本中的BA、C4和成纤维细胞生长因子19（FGF19）浓度。结果显示，CRC患者的初级和次级胆汁酸、C4和FGF19显著低于年龄和性别匹配的对照者（P < 0.05）。CDCA使HCT116和HT-29细胞中EdU阳性细胞的百分比分别降低了53.6%和28.3%（P < 0.001），并使HCT116和HT-29细胞的伤口闭合率分别降低了0.31±0.05倍和0.30±0.06倍（P < 0.05）。它使HCT116和HT-29细胞中的球体形成分别显著减少了90.0%和94.3%（P < 0.0001），并下调了CRC细胞中与EMT相关的干细胞标志物。胆汁酸合成和循环的失调可能有助于CRC的致癌作用。CDCA可能改变EMT，预防CRC的发生和发展。血浆胆汁酸在CRC预后中的预测作用及其在CRC预防和管理中的潜力应进一步探索。
