Abstract 1455: Knock down of the aryl hydrocarbon receptor sensitizes human breast carcinoma cell lines to radio- and chemotherapy

Abstract

Abstract Breast cancer is the most common cancer in North American women and is the second leading cause of cancer deaths in women today. Despite recent advances in treatment of breast cancer the development of chemo- and radio-resistance remains a major obstacle in treating advanced breast cancer. The aryl hydrocarbon receptor (AhR) is overexpressed and constitutively activated in several human breast carcinoma cell lines and the expression levels showed strong correlation with the degree of the tumor malignancy. In the current study, we evaluated the effect of reducing AhR expression on the chemo- and radio-sensitization of the MDA-MB231 human breast cancer cell line. We stably knocked down (KD) AhR expression in MDA-MB231 by using retroviral vectors expressing AhR-specific shRNA. Results show that reducing AhR expression enhanced radiation-induced apoptosis as shown by FITC-annexin V assay as well as significantly reducing cell clonogenic survival of MDA-MB231 cell line. In addition, knockdown of AhR alone has significantly impacted expression of genes regulating apoptotic pathways in these cells; increasing the expression of a number of pro-apoptotic genes while anti-apoptotic genes were down-regulated. Furthermore, the AhR-KD MDA-MB231 cells were sensitized to paclitaxol treatment; seen as an increase in the dose-dependent cytotoxicity compared to control cells. Our results suggest that reduction of AhR expression increases the chemo- and radio-sensitivity of MDA-MB231 breast cancer cell line. Therefore, AhR could be a novel target for enhancing efficacy of chemo and radiotherapy of breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1455. doi:1538-7445.AM2012-1455