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Resolvin E1 Reduces Tumor Growth in a Xenograft Model of Lung Cancer

      Inflammation plays a significant role in carcinogenesis and tumor growth. We tested the hypothesis that resolvin E1 (RvE1) and overexpression of the receptor for RvE1 (ERV1) will prevent and reverse tumor generation in a gain-of-function mouse model of tumor seeding with lung cancer cells. To measure the impact of enhanced resolution of inflammation on cancer pathogenesis, ERV1-overexpressing transgenic (TG) and wild-type FVB mice received an injection of 1 × 106 LA-P0297 cells subcutaneously and were treated with RvE1 (100 ng; intraperitoneally) or placebo. To assess the impact of RvE1 as an adjunct to chemotherapy, ERV1-TG and wild-type FVB mice were treated with cisplatin or cisplatin + RvE1. RvE1 significantly prevented tumor growth and reduced the tumor size, cyclooxygenase-2, NF-κB, and proinflammatory cytokines; these results were significantly greater in TG animals. A significant decrease in Ki-67, vascular endothelial growth factor, angiopoietin (Ang)-1, and Ang-2 was observed. Because ERV1 is only overexpressed on myeloid cells, we measured the actions of the transgene on tumor-associated-neutrophils and macrophages, which were significantly reduced by RvE1 (P < 0.001). RvE1 treatment led to a significant reduction of tumor volume and reduced expression of cyclooxygenase-2, NF-κB, vascular endothelial growth factor-A, Ang-1, and Ang-2 when administered together with cisplatin. The data suggest that RvE1 prevents inflammation and vascularization, reduces tumor seeding and tumor size, and, when used as an adjunct to chemotherapy, enhances tumor reduction at significantly lower doses of cisplatin.
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