Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies. Over 70% of ESCC cases occur in China. Unfortunately, the treatment of ESCC has hardly been improved all these years. Several studies suggested that aspirin (ASA) might decrease the risk of ESCC and prolonged the survival of patients with ESCC. However, it is unclear if ASA could prevent ESCC and/or enhance ESCC treatment by chemotherapy. In this study, a N-nitroso-N-methylbenzylamine (NMBzA) - induced ESCC model was employed to prove that aspirin could prevent the growth of esophageal tumor. F344 rats were treated with NMBzA by subcutaneous injection with or without ASA in drinking water (2mg/ml). After 35 week ASA-NMBzA or NMBzA alone treatment, rats were killed and esophageal tumor development were examined. The results showed that F344 rats treated with NMBzA and receiving a daily intake of ASA developed much less tumors than F344 rats treated with NMBA alone both in amount and in size (Tumor count: 2.40 ± 1.57 vs 10.85 ± 3.86 , P < 0.001; Tumor volume: 11.10 ± 13.38 mm3 vs 70.79 ± 41.65 mm3, P < 0.001). Immunohistochemical analysis indicated that a higher rate of apoptosis was observed in the basal layer of esophageal epithelium in ASA-NMBzA treated rats than in NMBzA alone treated rats. These results indicated that ASA prevented development of esophageal tumors in rats induced by NMBzA. Moreover, using in vitro human ESCC cell culture and in vivo xenograft models, we showed that ASA has strong beneficial effects on inhibition of ESCC cell proliferation and colony formation, reduction of ESCC cancer stem cells and enhance of ESCC cell cytotoxicity induced by cisplatin treatment. Biochemical analysis revealed that these effects of ASA on human ESCC cells in vitro and in vivo were due to inhibiting the repairing of DNA damage, decreasing the efflux activity and ALDH1 activity of the tumor cells, and blockades of PI3K/Akt pathway. Thus, our results demonstrated a positive role of aspirin in the prevention and treatment of ESCC.
Note: This abstract was not presented at the meeting.
Citation Format: Zhigeng Zou, Hongjun Fan, Xiying Yu, Shuming Zhang, Liping Guo, Wei Jiang, Shih-Hsin Lu. Aspirin inhibits the carcinogenesis of esophageal squamous cell carcinoma and enhances its responses to cisplatin [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1262. doi:10.1158/1538-7445.AM2017-1262