Heterophyllin B (HB) is a cyclic lipopeptide that has been shown to have anticancer effects. This study intended to further explore the effects and modulatory mechanism of HB in gastric cancer (GC) cells. The binding relationship between HB and CXCR4 was investigated by network pharmacological analysis, molecular docking, and cellular thermal shift assay (CETSA)-WB assay. Cellular assays revealed that HB could restrain GC cell viability, proliferation, invasion and migration by binding to CXCR4. Further studies presented that HB could suppress PI3K/AKT signaling pathway via binding to CXCR4, thus repressing PD-L1 expression. In vivo experiments in nude mice demonstrated that HB constrained PI3K/AKT signaling pathway to suppress GC cell metastasis and PD-L1 expression. In summary, the key target of HB in GC treatment was CXCR4. Cell experiments were employed for the investigation of the mechanism by which HB repressed GC cells. The results confirmed that HB could constrain the malignant progression of GC by the binding of HB into CXCR4 and suppressed PD-L1 expression via hampering PI3K/AKT signaling pathway.
Keywords: CXCR4; Gastric cancer; Heterophyllin B; Network pharmacology; PD-L1.
© 2022. The Author(s) under exclusive licence to Japan Human Cell Society.