Abstract 5478: EC-18 suppressed tumor growth and alleviated side effects caused by cisplatin in the HNSCC implantation model

Abstract

Abstract Introduction: Head and neck squamous cell carcinomas (HNSCC) are very unfavorable carcinoma that lowers the quality of life. In addition, side effects associated with treatment such as oral mucositis also deteriorate enough to be classified as a disease. This study verified the synergistic antitumor effect of EC-18 (PLAG, 1-Palmitoyl-2-linoleoyl-3-acetyl-roc-glycerol) with or without cisplatin as a chemotherapy and side effects alleviation effects in the metastatic mouse oral squamous carcinoma (MOSCC) orthotopic model. Method: After inserting mouse-derived squamous oral carcinoma into the right side of the tongue (n=12), it was treated with EC-18 alone or with cisplatin for three weeks. The changes in feed rate and body weight were quantitatively verified on a 2-day interval. Changes in tumor size and oral mucositis symptoms (toluidine-blue positive) were analyzed on the sacrifice day. In addition, changes in the amount of damage-associated molecular pattern (DAMP) increased by tumor and cisplatin, and changes in related active factors were quantitatively analyzed. Result: Compared to the positive control group, the tumor size was reduced by 42% in the group treated with EC-18 alone (P<0.05). In addition, the tumor size was further reduced by 25% in the group co-treated with EC-18 and cisplatin compared to the cisplatin alone (P<0.05), and it was observed that the tumor was disappeared in 3 mice in the co-treated group. In the positive control group, feed rate and body weight gradually decreased after about 12 days. Also, in the cisplatin-treated group, feed rate and body weight decreased rapidly after six days. On the other hand, in the group treated with EC-18 alone, there was no decrease in body weight and diet, and in the treatment with cisplatin, the diet and body weight gradually recovered after 14 days. Unlike the occurrence of oral mucositis symptoms independent of tumor growth inhibition by cisplatin, simultaneous treatment with EC-18 recovered oral mucositis symptoms along with the reduction of tumor growth (P<0.05). This effect could be explained by the fact that the expression of inflammation-related factors (TNFalpha, IL-1beta, IL-6) and DAMP (HMGB1, Adenosine) were effectively controlled by EC-18 (P<0.05). Conclusion: EC-18 can effectively inhibit the growth of HNSCC and alleviate the side effects caused by existing anticancer drugs at the same time. Therefore, it can be a desirable therapy for HNSCC patients. Citation Format: Guentae KIM, Eun Young Kim, Su-Hyun Shin, Hyowon Lee, Sun Young Yoon, Kaapjoo Park, Ki-young Sohn, Jae Wha Kim. EC-18 suppressed tumor growth and alleviated side effects caused by cisplatin in the HNSCC implantation model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5478.