1. Academic Validation
  2. Modulation of aryl hydrocarbon receptor inhibits esophageal squamous cell carcinoma progression by repressing COX2/PGE2/STAT3 axis

Modulation of aryl hydrocarbon receptor inhibits esophageal squamous cell carcinoma progression by repressing COX2/PGE2/STAT3 axis

  • J Cell Commun Signal. 2020 Jun;14(2):175-192. doi: 10.1007/s12079-019-00535-5.
Peiyao Zhu 1 Kun Zhou 1 Shilong Lu 2 Yu Bai 1 Ruiqun Qi 3 Shuguang Zhang 4
Affiliations

Affiliations

  • 1 Department of Thoracic Surgery, The First Hospital of China Medical University, No.155 North Nanjing Street, Shenyang, 110001, China.
  • 2 Department of Otolaryngology, Dermatology, Pathology, University of Colorado Anschutz Medical Campus, 12700 E 19th Avenue, Aurora, CO, 80045, USA.
  • 3 Department of Dermatology, The First Hospital of China Medical University, No.155 North Nanjing Street, Shenyang, 110001, China. xiaoqiliumin@163.com.
  • 4 Department of Thoracic Surgery, The First Hospital of China Medical University, No.155 North Nanjing Street, Shenyang, 110001, China. shgzhang@cmu.edu.cn.
Abstract

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.

Keywords

AHR; COX2; ESCC; PGE2; STAT3.

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