Genome-wide transcript profiling of human prostate stromal cells in response to genotoxic treatment and SASP inhibitors
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ABSTRACT: Cancer develops in a complex environment that encompasses a wide spectrum of benign cell types, while the local microenvironment reduces the efficacy of multiple forms of cancer therapies. The DNA damage secretory program (DDSP) provoked by the side effects of genotoxic therapeutics results in cellular senescence and the senescence-associated secretory phenotype (SASP), the side effects of the latter frequently fueling advanced pathologies particularly therapeutic resistance. However, candidate approaches to prevent or circumvent the SASP development remains limited. We treated PSC27, a primary normal human prostate stromal cell line, with the genoxotic agents hereby represented by bleomycin, to investigate the relevant mechanisms. In order to control the SASP development, a group of potential SASP inhibitors were applied including p38MAPK, mTOR and TAK1 suppressors. The purpose was to compare the efficacy and effectiveness of these chemicals in combinatin with typical anticancer drugs in minimizing the secretory phenotype upon DNA damage that functionally remodels human stromal cells.
ORGANISM(S): Homo sapiens
PROVIDER: GSE90866 | GEO | 2018/12/27
REPOSITORIES: GEO
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