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.

中文翻译：

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芳烃受体的调节通过抑制 COX2/PGE2/STAT3 轴来抑制食管鳞状细胞癌的进展。

食管鳞状细胞癌（ESCC）是最常见的恶性肿瘤之一，预后较差。芳基烃受体 (AHR) 是一种配体依赖性转录因子，新出现的证据表明它与肿瘤的发生和促进有关。然而，AHR 与 ESCC 之间的关系尚不清楚，探索 AHR 是否可以作为治疗靶点具有重要意义。在本研究中，进行了免疫组织化学以确定 ESCC 组织中的 AHR 表达水平。ESCC 细胞系中 AHR 表达的基因敲低和 3, 3'-二吲哚基甲烷 (DIM) 在体外和体内药理学上对 AHR 的调节被用于检查细胞生长、迁移和侵袭的相应变化。我们的研究表明 AHR 表达水平在 ESCC 中升高并且与预后不良相关。AHR 的敲低和调节均通过下调 PCNA、Bcl-2、Cyclin D1、MMP1、MMP2、MMP9 的表达水平和上调 Bax、Cleaved-Caspase 3 的表达水平来抑制肿瘤进展。我们的研究结果还表明，抑制COX2/PGE₂ /STAT3 轴在体外和体内试验中均对 ESCC 产生抑制作用。总之，AHR 在 ESCC 进展中起着关键作用，将 AHR 作为 DIM 的治疗策略值得进一步探索。