Chenodeoxycholic acid suppresses colorectal cancer by activating Farnesoid X receptor.

Colorectal cancer (CRC) is a major cause of cancer-related mortality worldwide. Therefore, it is critical to identify accurate biomarkers for improving early diagnosis and clinical outcomes. In our study, serum was collected from 90 healthy controls and 98 CRC patients after 8-hour fasting, followed by the measurement of chenodeoxycholic acid (CDCA) levels using ELISA. Cell proliferation and metastasis were assessed using MTT, colony-forming, and transwell assays. Farnesoid X receptor (FXR) was silenced with shFXR lentivirus, and its expression in tumors was analyzed by RT-qPCR. The result revealed that serum CDCA levels were significantly lower in CRC patients compared to healthy controls. Lower CDCA levels were associated with advanced TNM stage, differentiation status, and lymph node metastasis. FXR mRNA was significantly downregulated in CRC tumors and was negatively correlated with tumor aggressiveness. Serum CDCA levels were positively correlated with tumor FXR mRNA expression, and higher FXR expression was associated with better 5-year overall survival. CDCA treatment significantly suppressed CRC cell proliferation and migration in a dose- and time-dependent manner, whereas FXR knockdown attenuated these inhibitory effects. These findings indicated that CDCA suppressed CRC progression by activating FXR and inhibiting Wnt/β-catenin signaling. This highlights the potential of CDCA and FXR as therapeutic targets for CRC.