Abstract 4154: 1-Palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) exhibits the therapeutic effect in chemoradiation-induced oral mucositis mouse model
Authors: Lee Ha-Reum , Choi Solji , Yang Kwang Hoon , Lee Do Young , Moon Byoung-Gon , Sohn Ki-Young , Yoon Sun Young , Kim Jae Wha 
Published: August 2018

Oral mucositis is a common complication of chemoradiation therapy and is often accompanied by erythema, ulceration, pain, weight loss. It could delay remission and limit the effectiveness of cancer therapy and increase the risk of infections. However, no specific therapy for protection against mucositis is currently available. In previous study, PLAG (1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol, acetylated diglyceride) was shown to exert a therapeutic effect with pegfilgrastim to treat chemotherapy-induced neutropenia by modulating neutrophil transmigration and chemotherapy-induced megakaryocyte/erythrocyte progenitor decrese was significantly alleviated following PLAG administration. In this study, we investigated the therapeutic effect of PLAG in 5-fluorouracil (5-FU) and radiation-induced oral mucositis mouse model. Following 5-FU (100 mg/kg) injection on Day 0, mice were exposed to whole-body irradiation with 1 Gy gamma-ray radiation on Day 2. In order to facilitate the risk of infection, tongue was scratched 0.2 cm wound at using the tip of an 18-gauge needle at an equal force and depth on Day 4. PLAG was orally administered at 250 mg/kg/day. 5-FU, Radiation and scratching-induced oral mucositis mice exhibited ulceration, fibrosis, and festering wounds. PLAG treatment group decreased ulcer formation and diminished the degree of wound festering form on Day 5. Although CCRT-induce mice declined 16% of body-weight, PLAG only suppressed 2% of body-weight compare to control mice on Day 8. PLAG supported to mouse survival and inhibited mucositis-induced inflammatory responses in the tongue and serum. For head only radiation, custom-made lead shield was used for mice to limit the radiation to the head. After 5-FU (100 mg/kg) injection, mouse's head were received 20 Gy x-ray radiation and PLAG was administrated with 250 mg/kg daily. In toluidine blue (TB) staining, PLAG suppressed concurrent chemoradiotherapy (CCRT)-induced oral mucositis and inflammatory responses. At Day 10, CCRT-induced oral mucositis mice were shown the weight loss and tongue wound festered, and had still not fully recovered and resulted in death. PLAG administration significantly reduced CCRT-induced mucositis and recovered scar better quicker. PLAG also decreased body-weight loss and increased mice survival rate. In histological analysis, CCRT-induced inflammation was recovered in PLAG-treated mice. These data suggest that PLAG enhances recovery from 5-FU/radiation-induced oral mucositis and cachexia. From these data, PLAG could be therapeutically useful in reducing the complications associated with chemotherapy and radiation, and thus may be an excellent supplementary agent for anti-cancer therapy.

Citation Format: Ha-Reum Lee, Solji Choi, Kwang Hoon Yang, Do Young Lee, Byoung-Gon Moon, Ki-Young Sohn, Sun Young Yoon, Jae Wha Kim. 1-Palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) exhibits the therapeutic effect in chemoradiation-induced oral mucositis mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4154.