Abstract 1: Sulindac plus phospholipid is effective for polyp reduction and safer than sulindac alone

Abstract

Abstract Purpose: To evaluate the chemoprevention efficacy and relative safety of sulindac combined with a phospholipid compared to sulindac alone. Methods: Apcmin/+ mice on the C57/B6 background were randomized to receive oral gavage of sulindac, sulindac combined with the phospholipid (phosphatidyl choline, sulindac-PC), saline or no treatment, daily for twenty-one days. At the end of the treatment period, polyp burden and gastric integrity were assessed in a blinded Following formalin fixation, the stomach from each animal was embedded in paraffin and sectioned for microscopic evaluation. In addition to mucosal ulceration, three measures of gastric inflammation were taken. To test biological activity of sulindac and sulindac-PC, nuclear β-catenin immunohistochemistry was performed on small intestinal polyps. Results: Both sulindac and sulindac-PC treated animals had significantly decreased polyp burden compared to controls (Table 1). Additionally, sulindac-PC treated mice had significantly (p=0.02) lower gastric inflammation scores (1.00 ± 0.63) compared to sulindac alone (2.14 ± 0.90). Two out of seven sulindac treated mice were found to have gastric ulcers, compared to zero out of six sulindac-PC treated mice, though this difference was not statistically significant. Both sulindac and sulindac-PC treated mice had significantly lower nuclear β-catenin staining compared to control treated mice (Table 1). Conclusions: Our findings suggest the addition of a phospholipid as an effective strategy to reduce gastric toxicity of non-steroidal anti-inflammatory drugs, such as sulindac, while maintaining chemopreventive efficacy. Citation Format: Jennifer Sarah Davis, Preeti Kanikarla, Patrick L. Yu, Mihai Gagea, Dexing Fang, Manu Sebastian, Peiying Yang, Ernest Hawk, Roderick Dashwood, Lenard M. Lichtenberger, David Menter, Scott Kopetz. Sulindac plus phospholipid is effective for polyp reduction and safer than sulindac alone [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1.