Research on Clinical Effectiveness of Aspirin for Treating Breast Cancer and Cell Protein Biomarkers on Aspirin Treatment in Drug-Resistant Estrogen Receptor-Positive Breast Cancer Cells

Abstract

Background: Aspirin (ASA) has been reported to have an antitumor effect but the role of ASA in the prevention and treatment of breast cancer (BC) is still controversial. This study aimed to identify clinical effectiveness of ASA in the treatment of BC and explore the antitumor target proteins of ASA that may be involved in overcoming tamoxifen resistance in estrogen receptor (ER)-positive BC cells. Materials and Methods: Randomized controlled trials (RCTs) of ASA in the treatment of BC were queried from the databases, including PubMed, Web of Science, Cochrane Library, WanFang, and Chinese National Knowledge Infrastructure. According to the quality standard recommended in the Newcastle-Ottawa Scale (NOS), the outcome indexes were analyzed by RevMan 5.3 and Stata 12.0 software. Cell culture experiments were performed to explore the effect of tamoxifen combined with ASA on the proliferation of ER-positive BC cell lines MCF-7 and MCF-7/TAM. Cell cytotoxicity was determined by the 3-(4, 5-di-2-yl)-2, 5-ditetrazolium bromide (MTT) assay. A quantitative proteomic analysis was conducted between the control and experimental groups to identify differentially expressed proteins (DEPs). Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used for bioinformatic analysis of DEPs. The protein expression in patients of ER-positive BC was analyzed by immunochemistry (IHC). Results: Nine RCTs including 162,381 patients were selected for this study. The meta-analysis revealed that daily ASA use, as compared with its non-use, was associated with a decreased risk of BC death: relative risk (RR) = 0.83%, 95% CI [0.73, 0.94], Z = 2.89, P = 0.004 (P