目的：研究芳香烃受体（AHR）在乳腺癌中的表达及其对乳腺癌细胞增殖、凋亡和药物敏感性的调控机制。方法：通 过GEPIA数据库数据分析乳腺癌组织及癌旁组织中AHR的表达水平，探讨其与患者生存期的关联。利用基因敲低和过表达技 术构建AHR表达变化的乳腺癌细胞，采用CCK-8实验、细胞计数和流式细胞分析等方法评估AHR对细胞增殖、凋亡和药物敏感 性的影响，通过免疫印迹法验证相关分子机制。此外，利用AHR激动剂6-甲酰基吲哚并[3,2-B]咔唑（FICZ）研究外源性激活AHR 对乳腺癌细胞多柔比星（DOX）敏感性的影响。结果：GEPIA 数据库数据分析结果显示，乳腺癌组织中 AHR呈明显低表达 （P < 0.05）；对155例乳腺癌患者的生存期进行统计分析也显示AHR低表达与不良预后呈正相关（P < 0.05）。敲低AHR促进细胞 增殖（P < 0.05），过表达则能抑制其增殖（P < 0.05）并促进其凋亡（P < 0.05）。外源激活AHR能增强乳腺癌细胞对DOX的敏感性 （P < 0.05）。AHR可与MYC基因启动子结合，抑制MYC表达（P < 0.05），从而影响乳腺癌的进展。结论：AHR在乳腺癌中通过 调控MYC表达影响细胞增殖和凋亡，外源激活AHR可能成为提高乳腺癌细胞对DOX敏感性的治疗策略。

Objective: To investigate the expression of aryl hydrocarbon receptor (AHR) in breast cancer and its regulatory mechanisms in the proliferation, apoptosis, and drug sensitivity of breast cancer cells. Methods: The GEPIA database was used to analyze the expression levels of AHR in tumor tissues and adjacent normal tissues of breast cancer patients and explore its correlation with patient survival. Gene knockdown and overexpression techniques were employed to establish breast cancer cell lines with varying AHR expression levels. The impact of AHR on cell proliferation, apoptosis, and drug sensitivity was evaluated using CCK-8 assays, cell counting, and flow cytometry. The molecular mechanisms were validated through WB. Additionally, the effect of exogenous AHR activation using the AHR agonist 6-Formylindolo[3,2-b] carbazole (FICZ) on the doxorubicin (DOX) chemosensitivity of breast cancer was investigated. Results: GEPIA database analysis revealed a significant decrease in AHR expression in breast cancer tissues (P < 0.05); statistical analysis of the survival data from 155 breast cancer patients also indicated that low AHR expression was associated with poor prognosis (P < 0.05). AHR gene knockdown promoted cell proliferation (P < 0.05), while overexpression inhibited proliferation (P < 0.05) and promoted apoptosis (P < 0.05). Exogenous AHR activation enhanced the sensitivity of breast cancer cells to DOX (P < 0.05). AHR was found to bind to the MYC promoter, suppressing MYC expression, thereby influencing the progression of breast cancer. Conclusion: AHR regulates cell proliferation and apoptosis in breast cancer by modulating MYC expression. Exogenous activation of AHR may serve as a promising therapeutic strategy to enhance the sensitivity of breast cancer cells to DOX.

天津市医学重点学科（专科）建设项目（No. TJYXZDXK015A）；天津市卫生健康科技项目（No. TJWJ2023QN030）