Aspirin Inhibits Tumor Progression And Enhances Cisplatin Sensitivity Of Epithelial Ovarian Cancer

Objective The purpose of this study was to investigate the effects of aspirin on migration,proliferation and cisplatin sensitivity of epithelial ovarian cancer(EOC) cells and to explore the underlying molecular mechanisms.Methods 1. The effects of aspirin on cell migration and proliferation were respectively examined by wound scratch assays, transwell migration assays, Ed U cell proliferation assays, and colony formation assays.2. MTT assays were used to assess the aspirin-induced alterarions in cisplatin cytotoxicity on EOC cells.3. Six-week-old female BALB/c-nu/nu mice were used to establish orthotopic xenograft models of ovarian cancer with A2780-Luciferase-GFP cells. Then the mice were randomized into three groups treated with intraperitoneal cisplatin(cisplatin group), intraperitoneal cisplatin combined with intragastric aspirin(combination group), and intraperitoneal saline combined with intragastric pure water(control group). The weight of mice was evaluated every other day. In vivo imaging was conducted every seven days.4. The expression and acetylation level of p53 in EOC cells treated with aspirin were detected by western blot. Quantitative real-time PCR was used to assess the m RNA expression of p53 target genes(p21, bax, foxf1, puma, and rad).Results1. Aspirin inhibited the migration and proliferation of A2780, OV2008, and C13K cells in a concentration-dependent manner.2. Aspirin decreased the cisplatin IC50 in EOC cell lines A2780, C13 K, and OV2008.3. The tumor growth inhibition rate in the cisplatin group, and the combination group were 49.3% and 78.4%, respectively. The difference in inhibition rate between the cisplatin group and the combination group was statistically significant(P<0.05).4. Aspirin did not affect p53 protein expression but increased p53 acetylation level in a concentration-dependent manner. The m RNA levels of p21, bax, foxf1, puma, and rad in EOC cells were significantly increased by aspirin treatment.Conclusion Aspirin can inhibit tumor progression and enhance cisplatin sensitivity of EOC. These anti-tumor effects of aspirin might be mediated by p53 acetylation and subsequent activation of p53 target genes regulating tumor migration, proliferation, and chemo-resistance. Further studies are needed to verify the role of p53 acetylation in the aspirin mediated anti-tumor effects.