Fuzheng Shengbai decoction enhances antitumor immunity via YTHDC2-dependent stabilization of CLCA2 mRNA in colorectal cancer.

[ETHNOPHARMACOLOGICAL RELEVANCE] Traditional Chinese medicine (TCM) has demonstrated multiple therapeutic advantages in colorectal cancer (CRC) management. The herbal formula Fuzheng Shengbai Decoction (FZSB) has been widely used in clinical practice with well-documented therapeutic efficacy; nevertheless, the mechanisms underlying its anti-CRC effects remain largely unexplored.

[AIM OF THE STUDY] To evaluate the therapeutic efficacy of FZSB in colorectal cancer and its potential underlying mechanisms.

[MATERIALS AND METHODS] Through both clinical and experimental studies, the therapeutic efficacy and underlying mechanisms of FZSB in colorectal cancer were investigated. A clinical cohort of postoperative CRC patients and BALB/c mouse xenograft models were used to evaluate its immunomodulatory and antitumor effects. RIP-qPCR, MeRIP-qPCR, and MeRIP-seq were employed to explore the potential molecular mechanisms of FZSB. Molecular docking was performed to assess the interactions between active components of FZSB and key targets.

[RESULTS] FZSB significantly inhibited CRC growth and proliferation both in vivo and in vitro. In the clinical cohort, FZSB elevated the CD4/CD8 T-cell ratio. In xenograft models, FZSB increased CD8 T-cell infiltration, proportion, and activation, and upregulated the tumor suppressor CLCA2, which was positively correlated with prognosis. Mechanistically, FZSB stabilized YTHDC2, promoting mA-dependent CLCA2 mRNA stabilization and expression. Molecular docking indicated that multiple FZSB bioactive compounds could interact favorably with YTHDC2 and CLCA2.

[CONCLUSIONS] FZSB enhances anti-colorectal cancer immune responses and is associated with increased CD8 T-cell activation, while concurrently modulating the YTHDC2-CLCA2 axis via mA -mediated mRNA stabilization.