Modulation of aryl hydrocarbon receptor inhibits esophageal squamous cell carcinoma progression by repressing COX2/PGE2/STAT3 axis
Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors with poor prognosis. Aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor and emerging evidence shows it is associated with tumor initiation and promotion. However, the relationship between AHR and ESCC is not clear and it is meaningful to explore whether AHR could be a therapeutic target. In the present study, immunohistochemistry was performed to determine AHR expression levels in ESCC tissues. Knockdown of AHR expression in ESCC cell lines genetically and modulation of AHR by 3, 3′-diindolylmethane (DIM) pharmacologically both in vitro and in vivo were utilized to examine the corresponding alterations in cell growth, migration and invasion. Our study indicated that AHR expression levels were elevated in ESCC and associated with poor prognosis. Both knockdown and modulation of AHR inhibited tumor progression through down-regulating expression levels of PCNA, Bcl-2, Cyclin D1, MMP1, MMP2, MMP9 and up-regulating expression levels of Bax, Cleaved-Caspase 3. Our findings also indicated that repressing COX2/PGE2/STAT3 axis exerted inhibitory effects on ESCC both in vitro and in vivo assays. Taken together, AHR plays the key role in ESCC progression and targeting AHR as a therapeutic strategy with DIM is deserved for further exploration.
KeywordsAHR COX2 ESCC PGE2 STAT3
Aryl hydrocarbon receptor
Cytochrome P450, family 1, member A1
Esophageal squamous cell carcinoma
Proliferating cell nuclear antigen
Signal transducer and activator of transcription 3
This work was supported in part by a grant from Department of Education of Liaoning Province (LK201614). We thank the NHC Key Laboratory of Immunodermatology (China Medical University) for experiments carried out. We also thank Professor Ruiqun Qi for experimental instructions.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interests.
All procedures performed in studies involving animals were in accordance with the ethical standards of the Animal Ethics and Experimental Committee of China Medical University (Approved number: 2018146).
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