Sijunzi Decoction Inhibits Sternness by Suppressing β-Catenin Transcriptional Activity in Gastric Cancer Cells

Objective: To investigate a previously uncharacterized function of Sijunzi Decoction (SJZD) in inhibition of gastric cancer stem cells (GCSCs). Methods: MKN74 and MKN45, two CD44 positive gastric cancer cell lines with stem cell properties were used. The cells were divided into 2 groups. Treatment group was treated with SJZD (1-5 mg/mL) for indicated time (48 h-14 days). The control group was treated with equal volume of phosphate buffered saline. Cell Counting Assay Kit-8 were used to measure cell viability. Spheroid colony formation and GCSCs marker expression were performed to determine GCSCs sternness. Cell fractionation and chromatin immunoprecipitation assays were used to assess the distribution and DNA-binding activity of beta -catenin after SJZD treatment, respectively. Results: SJZD treatment repressed cell growth and induced apoptosis in MKN74 and MKN45 cell lines (P<0.05). Moreover, SJZD dramatically inhibited formation of spheroid colony and expression of GCSC markers in GC cells (P<0.05). Mechanistically, SJZD reduced nuclear accumulation and DNA binding activity of beta -catenin (P<0.05), the key regulator for maintaining CSC sternness. Conclusion: SJZD inhibits GCSCs by attenuating the transcriptional activity of beta -catenin.

Automated summary

SJZD inhibits the development and proliferation of gastric cancer stem cells by attenuating the transcriptional activity of beta-catenin.