L-4F suppresses pancreatic cancer progression associate with inhibiting inflammation in mouse pancreatic cancer model
作者单位：Weifang Medical University Tianjin Medical University
会议名称：《第十届全国免疫学学术大会》
会议日期：2015年
学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100214[医学-肿瘤学] 10[医学]
关 键 词：Pancreatic cancer L-4F Inflammation STAT3 MAPK
摘 要：Objective: Pancreatic cancer is an aggressive malignancy and unresponsive to conventional radiation and chemotherapies. Therefore, the development of novel immune therapeutic strategies is urgently needed. In this study, the antitumor effects and anti-inflammatory properties of L-4F, an Apo A-I mimetic peptide, engineered to mimic anti-inflammatory and anti-oxidant functionalities of Apo A-I, on pancreatic cancer were ***: In the in vitro study, the effects of L-4F on invasion, proliferation and apoptosis of mouse pancreatic cancer H7 cells were assessed after L-4F treatment. In the in vivo study, H7 cells were orthotopic implanted in C57BL/6 mice and treated with L-4F, the effects of L-4F on tumor development and anti-inflammation were investigated. In addition, we utilized Lipopolysaccharide-stimulated murine macrophage cell line RAW 264.7 as inflammatory model to test the anti-inflammatory mechanism of L-4F. Results: Results show that L-4F substantially reduced the tumorigenicity of H7 cells. It was associated with inhibiting tumor angiogenesis and inflammation via reducing the accumulation of inflammatory cells, such as IL-17, GM-CSF, IL-1β, IL-6-producing cells and Th1, Th17. However, L-4F could not attenuate H7 cell invasion, proliferation and induced apoptosis. In addition, L-4F decreases the production of inflammatory cytokines, TNF-α and IL-6, by up-regulating STAT3 and down-regulating MAPK signaling pathways. Conclusions: These results suggest that L-4F elicits an effective therapeutic effect on pancreatic cancer progression by inhibiting tumor angiogenesis and inflammation.