Xiaotan Sanjie recipe suppressed the oncogenic potential of cancer-associated fibroblaststhe stromal-derived factor 1α/C-X-C chemokine receptor type 4 pathway in gastric cancer.

OBJECTIVE

To investigate the impact and mechanism of action of Xiaotan Sanjie (, XTSJ) on the invasiveness and metastasis of gastric cancer (GC) by modulating cancer-associated fibroblasts (CAFs). MKN-45 cells were used in in vitro experiments, and an in vivoxenograft model was established for further analysis.

METHODS

Two types of fibroblasts, CAFs and normal fibroblasts, were isolated from the tissue sample of two patients following GC surgery. The in vitro and in vivoexperiments were treated with XTSJ. Immun-ohistochemistry and enzyme-linked immunosorbent assay (ELISA) were used to assess levels of Vimentin, α-smooth muscle actin, and C-X-C chemokine receptor type 4 (CXCR4). The quantities of interleukin-6 (IL-6), stromal-derived factor 1α (SDF-1α), vascular endothelial growth factor (VEGF), and interleukin-1β (IL-1β) were measured using quantitative real-time polymerase chain reaction and ELISA.

RESULTS

The results indicated that CAFs significantly enhance the migration and invasion of GC cells compared to NFs. However, following treatment with XTSJ, CAF's ability to promote GC was reduced. XTSJ treatment significantly inhibited CAF proliferation and downregulated the expression of CAF-associated cytokines IL-1β, IL-6, VEGF, and SDF-1α. The SDF-1α/ CXCR4 signaling pathway is a potential key mechanism through which CAFs impact GC invasion.

CONCLUSION

XTSJ treatment inhibited tumor-promoting capabilities in CAFs, suppressing GC progression, invasion, and metastasis. This study offers empirical support for the potential clinical application of XTSJ in treating and preventing GC metastasis.