Gender disparity has long been considered as a key to fully understand hepatocellular carcinoma development. At the same time, immunotherapy related to interleukin-12 still need more investigation before applied in clinical settings. The aim of this study is to investigate the influence of androgen receptor (AR) on natural killer (NK) cells related innate immune surveillance in liver cancer, and provide a novel therapeutic approach to suppress hepatocellular carcinoma (HCC) via altering IL-12A. By using in vitro cell cytotoxicity test and in vivo liver orthotopic xenograft mice model, we identified the role of AR in modulating NK cells cytotoxicity. Luciferase report assay and chromatin immunoprecipitation assay were applied for mechanism dissection. Immunohistochemistry is performed for sample staining. Our results showed AR could suppress IL-12A expression at the transcriptional level via direct binding to the IL-12A promoter region that resulted in repressing efficacy of NK cell cytotoxicity against HCC, and sorafenib treatment could enhance IL-12A signals via suppressing AR signals. These results not only help to explain the AR roles in the gender disparity of HCC but also provide a potential new therapy to better suppress HCC via combining sorafenib with NK cells related immunotherapy.
from Cancer via ola Kala on Inoreader http://ift.tt/1QwBNsX
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