β‐Sitosterol as an Anti‐Tumour Active Component of Herba Sarcandrae Inhibits Colorectal Cancer Progression Through Up‐Regulation of TBX20

ABSTRACT Colorectal cancer (CRC) is a common malignant tumor of the digestive tract with a high incidence rate. Herba Sarcandrae (HS) is an antipyretic and has been reported to have anti‐cancer effects. This study explored the impacts of β‐sitosterol on the sensitivity of CRC to 5‐fluorouracil (5‐FU) and oxaliplatin and the stability of TBX20 protein in CRC cells. There were 41 HS active ingredients and 265 corresponding potential targets, and 48 potential targets of HS were enriched in CRC. Then, 206 differentially expressed genes (DEGs) related to TBX20 overexpression were screened based on the TCGA database, some of which were associated with TMN stages of COAD patients. Epimedin C, rutin, and β‐sitosterol, which could be combined with TBX20, were screened and validated in CRC cells. Functionally, β‐sitosterol could suppress proliferation and induce apoptosis of CRC cells. β‐sitosterol could also enhance the sensitivity of CRC to 5‐FU and oxaliplatin. In xenograft models, both HS and β‐sitosterol treatments inhibited tumor growth and upregulated TBX20 protein expression, with β‐sitosterol demonstrating a stronger effect. Mechanistically, β‐sitosterol may stabilize TBX20 by inhibiting its ubiquitin‐mediated degradation. In conclusion, β‐sitosterol, as an anti‐tumor active component of HS, prevents CRC cell proliferation, and accelerates apoptosis by upregulating TBX20.