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Updated: Jul 24, 2025
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Published on: May 9, 2020
Celastrol inhibits gastric cancer cell proliferation, migration, and invasion via the FOXA1/CLDN4 axis
Wei Peng1, Lin Chen2, Jie Liu1
1Changsha Social Work College, Changsha 410018, Hunan Province, China.
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.
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.
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.
Insights
Celastrol inhibits gastric cancer (GC) progression by targeting the FOXA1/CLDN4 axis, which impedes the PI3K/AKT pathway. This study reveals a novel mechanism for celastrol
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Celastrol exhibits potent anti-tumor properties.
- The precise mechanism of celastrol's action in gastric cancer (GC) remains unclear.
Purpose of the Study:
- To elucidate the specific mechanism by which celastrol affects GC cells.
- To investigate the role of forkhead box A1 (FOXA1) and claudin 4 (CLDN4) in celastrol's anti-GC effects.
Main Methods:
- GC cells were manipulated for FOXA1 and CLDN4 expression.
- Quantitative reverse transcription PCR and Western blot analyzed gene and protein expression.
- Cell proliferation, migration, invasion, and FOXA1-CLDN4 interaction were assessed using MTT, Transwell, and luciferase reporter assays.
Main Results:
- Celastrol downregulated FOXA1, inhibiting GC cell proliferation, migration, and invasion.
- Overexpression of FOXA1 or CLDN4 accelerated GC progression.
- CLDN4 overexpression activated the PI3K/AKT pathway, and FOXA1 enhanced CLDN4 transcription.
Conclusions:
- Celastrol targets the FOXA1/CLDN4 axis to inhibit GC progression by impeding the PI3K/AKT pathway.
- This research provides a new understanding of celastrol's anti-GC mechanism.
- Findings support the potential of celastrol as an anti-gastric cancer therapeutic.
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