Aspirin inhibits tumor progression and enhances cisplatin sensitivity in epithelial ovarian cancer

Jianfeng Guo; Yapei Zhu; Lili Yu; Yuan Li; Jing Guo; Jing Cai; Lin Liu; Zehua Wang

doi:10.7717/peerj.11591

Aspirin inhibits tumor progression and enhances cisplatin sensitivity in epithelial ovarian cancer

PeerJ. 2021 Aug 2:9:e11591. doi: 10.7717/peerj.11591. eCollection 2021.

Authors

Jianfeng Guo^#¹, Yapei Zhu^#¹, Lili Yu¹, Yuan Li¹, Jing Guo¹, Jing Cai¹, Lin Liu¹, Zehua Wang¹

Affiliation

¹ Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

^# Contributed equally.

Abstract

Background: Ovarian cancer is the most common gynecological malignancy and is difficult to manage due to the emergence of resistance to various chemotherapeutic drugs. New efforts are urgently awaited. Aspirin, which is traditionally considered a nonsteroidal anti-inflammatory drug (NSAID), has been reported to exert potential chemopreventive effects. Therefore, we aimed to investigate the anticancer effect and explore the underlying molecular mechanisms of aspirin on epithelial ovarian cancer (EOC) cells.

Methods: We conducted wound healing, transwell migration, EdU cell proliferation, colony formation and apoptosis detection assays to observe the effects of aspirin on the migration, proliferation and apoptosis of EOC cells (A2870, Caov-3, and SK-OV-3). EOC cells were treated with a combination of aspirin and cisplatin (CDDP) to observe the effect of aspirin on enhancing CDDP sensitivity. Orthotopic xenograft models of ovarian cancer established with A2780-Luciferase-GFP cells were applied to compare tumor growth inhibition in the control, CDDP and CDDP plus aspirin groups through in vivo imaging, which can be used to continuously monitor tumor growth. The expression and acetylation levels of p53 in EOC cells treated with aspirin were determined using western blotting, and p53 acetylation levels were examined in tumors harvested from the transplanted mice. Quantitative real-time PCR was used to assess the mRNA expression of p53 target genes.

Results: Aspirin inhibited migration and proliferation and induced apoptosis in EOC cell lines in a concentration-dependent manner. In vitro, aspirin enhanced the sensitivity of EOC cells to CDDP by increasing its inhibitory effect on proliferation and its effect on inducing apoptosis. In vivo, the differences in the tumor growth inhibition rates among the different CDDP experimental groups were statistically significant (p < 0.05). Aspirin did not affect p53 protein expression but increased the p53 acetylation level in a concentration-dependent manner. In addition, the mRNA levels of CDKN1A, BAX, FOXF1, PUMA, and RRAD in EOC cells were significantly increased by the aspirin treatment.

Conclusions: Aspirin inhibits tumor progression and enhances the CDDP sensitivity of EOC cells. These antitumor effects of aspirin might be mediated by p53 acetylation and subsequent activation of p53 target genes.

Keywords: Acetylation; Aspirin; Cisplatin; Ovarian cancer; p53.

Grants and funding

This work was supported by the National Natural Science Foundation of China (No. 81672573). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.