Tumor Suppressor Role of Aryl Hydrocarbon Receptor in Cervical Cancer

The aryl hydrocarbon receptor (AhR) plays a pivotal role in tumorigenesis; however, its role in cervical cancer is unclear. This study investigated the function of AhR in cervical cancer by analyzing AhR mRNA expression in tumors and adjacent normal tissues from patients and cervical cancer cell lines using RT-qPCR. AhR was overexpressed in cervical cancer cell lines using lentiviral vectors, and its effects on cell viability, colony formation, cell cycle, apoptosis, and migration/invasion were evaluated. Western blot analysis was used to assess the impact of AhR on the expression of apoptosis genes and epithelial-to-mesenchymal transition (EMT)-related genes. We established a mouse xenograft model to evaluate the effects of AhR on cervical cancer tumorigenesis. AhR expression was downregulated in both patient tissues and cell lines. AhR overexpression reduced cell viability, colony formation, and migration/invasion, induced cell cycle arrest and apoptosis in cervical cancer cells, and suppressed tumor growth and weight in the xenograft model. Immunohistochemical analysis confirmed reduced cell proliferation and increased apoptosis in the HeLa xenografts. AhR overexpression downregulated cell survival and EMT-promoting genes, and upregulated apoptosis-promoting and EMT-suppressing genes. AhR is a crucial tumor suppressor in cervical cancer, suggesting potential therapeutic implications for its upregulation in cervical cancer management.