Constitutive AhR activation leads to concomitant ABCG2‐mediated multidrug resistance in cisplatin‐resistant esophageal carcinoma cells

Authors:
Publisher website
Google Scholar
Abstract
Esophageal squamous cell carcinoma (ESCC) is a highly malignant disease that is generally not responding to chemotherapy. It is particularly predominant in China. Although ESCC is significantly associated with cigarette smoking, the relationship between its molecular pathogenesis and responsiveness to chemotherapy and cigarette smoke remains elusive. This study reported the constitutive activation of aryl hydrocarbon receptor (AhR), leading to ABCG2 upregulation and the multidrug resistance (MDR) phenotype, in ESCC cell lines with acquired cisplatin resistance. Reporter gene assay, chromatin immunoprecipitation analysis and specific gene knockdown confirmed that the enhanced AhR binding to a xenobiotic response element (XRE) within the ABCG2 promoter is responsible for ABCG2 overexpression. A HSP90 inhibitor (17‐AAG) and two AhR antagonists (kaempferol and salicylamide) were shown to inhibit ABCG2 upregulation, thereby reversing the ABCG2‐mediated MDR. Our data therefore advocate the use of these inhibitors as novel chemosensitizers for the treatment of esophageal cancer.

This publication has 42 references indexed in Scilit: