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Aryl hydrocarbon receptor modulates the proliferation, apoptosis and sensitivity to doxorubicin of breast cancer cells by suppressing MYC expression
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Abstract:
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.
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