Ott_a_215824 7611..7621

Su-Ya Hsu Hui-Yuan Yu Wei-Chen Lee Chia-En Hsiao Chih-Lung Wu Hsi-Tsung Cheng Li-Jin Lin Fang Li Yu-Ting Chou Jya-Wei Cheng 1Department of Medical Science, Institute of Biotechnology, National Tsing Hua University, Hsinchu 300, Taiwan; 2Division of Cancer Research, Rise Biopharmaceuticals Inc., Zhongguancun Shangdi Bio-medical Park, Beijing 100085, People’s Republic of China; 3Department of Immunology, Dalian Medical University, Dalian 116044, People’s Republic of China Purpose: Lung cancer and other solid tumors contain not only tumor cells but various types of stromal cells, such as fibroblasts and endothelial cells. In addition, tumors are infiltrated by inflammatory cells (neutrophils, macrophages, and lymphocytes). Tumor cells, stromal cells, and the tumor-associated leukocytes are responsible for the production of chemokines inside the tumor and the maintenance of systemic circulating chemokine levels. CXCL8 and its receptors, CXCR1 and CXCR2, were found to play important roles in tumor proliferation, migration, survival, and growth. We have developed a novel ELR-CXC chemokine antagonist CXCL8-IP10 based on the structure of CXCL8 and IP10. Patients and methods: We assessed the anticancer efficacies of the blockade of CXCL8CXCR1/2 axis in the Lewis lung carcinoma (LL/2) model using CXCL8-IP10. Results: We found that CXCL8-IP10 markedly reduced LL/2 cell anchorage-independent growth and invasion. Moreover, we demonstrated that CXCL8-IP10 could significantly suppress tumor growth and improve survival rate as well as lifespan of C57BL/6 mice inoculated with LL/2 cells. Conclusion: Our results suggest that ELR-CXC chemokine antagonism would potentially be a useful therapeutic approach in patients with lung cancer.