Nicaraven prevents the fast growth of inflamed tumors by an anti-inflammatory mechanism

Inflammatory microenvironment is known to accelerate the progression of malignant tumors. We investigated the possible anti-inflammatory effect of nicaraven on slowing tumor growth. Tumor-bearing mice randomly received nicaraven injection (50 mg/kg daily, i.p, n = 8) or placebo treatment (n = 8) for 10 days, and then sacrificed for evaluations. Nicaraven administration effectively inhibited the fast growth of tumor, as a large tumor (> 1.0 g) developed finally in three of the eight mice received placebo treatment. Cytokines/chemokines array indicated that nicaraven reduced the levels of CXCL10 and SDF-1 in the tumor as well as the levels of IL-2 and MIP-2 in serum. Immunofluorescence staining showed that nicaraven significantly reduced the recruitment of macrophages and neutrophils in the tumor. Interestingly, western blot indicated that the expression of CD86, CD206, and NIMP-R14 was especially enhanced in the three large-size tumors, suggesting the potential role of nicaraven in preventing the hyper-inflammatory tumor microenvironment. Moreover, the expression of PARP-1 was downregulated, but the expression of phospho-p38 MAPK, phospho-MKK-3/6, and phospho-MSK-1 was upregulated in the large-size tumors, suggesting the involvement of p38 MAPK pathway in the anti-inflammatory effect of nicaraven. Taken together, our study suggests that nicaraven may effectively prevent the fast growth of inflamed tumors by an anti-inflammatory mechanism.