Background
Celastrol is a biologically active compound with potent anti-tumor properties. However, the mechanism of action of celastrol in gastric cancer (GC) has not been fully elucidated.
Conclusion
Celastrol regulated GC progression via targeting the FOXA1/CLDN4 axis to impede the PI3K/AKT pathway. Our study proposed a new mechanism of how celastrol inhibited tumorigenesis in GC, which provided evidence for the potential use of celastrol for anti-GC treatment.
Methods
To explore the specific mechanism of the effect of celastrol on GC cells. GC cells were transfected with forkhead box A1 (FOXA1) or claudin 4 (CLDN4), or short hairpin RNA targeting FOXA1. The expressions of FOXA1 and CLDN4 in GC cells were determined by quantitative reverse transcription PCR and Western blot. GC cell proliferation, migration, and invasion were measured by MTT assay and Transwell assay, respectively. The interaction between CLDN4 and FOXA1 was examined by luciferase reporter assay. Resluts: CLDN4 and FOXA1 were upregulated in GC cells. Celastrol prevented the proliferation, migration, and invasion of GC cells by downregulating FOXA1 expression. Overexpression of FOXA1 or CLDN4 accelerated GC progression. CLDN4 overexpression also induced the activation of the expressions of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway. FOXA1 enhanced the transcription of CLDN4.