Vasoactive intestinal peptide represses activation of tumor-associated macrophages in gastric cancer via regulation of TNFα, IL-6, IL-12 and iNOS.

Vasoactive intestinal peptide (VIP) has been regarded as deactivator for macrophages. However, the depressive effect of VIP on tumor-associated macrophages (TAM) has not been recognized. In the present study, we investigated the effect of VIP on gastric cancer via TAM by suppressing expression levels of TNFα, IL-6, IL-12 and iNOS. Real-time PCR was carried out to examine the expression of CD68 to determine the levels of TAM. The effect of VIP on cell activities was assayed by proliferation assay, colony formation and flow cytometry analysis. The co-culture of TAM and human gastric cancer cell line MKN-45 were performed to understand whether the VIP affects the gastric cancer cells via TAM. Further, the tumor formation in a nude mouse model and VIP injection were performed to illustrate the effect on tumor progression in vivo. CD68 was high expressed in gastric cancer indicating high level of TAM in gastric cancer. Treatment with VIP significantly depressed TAM activation. Moreover, the expression of TNFα, IL-6, IL-12 and iNOS in TAM were depressed by VIP treatment, and the VIP treated TAM depressed gastric cancer cells. The experiment in the nude mouse model also suggested that by injection with TAM+VIP, the tumor volume and tumor weight were both decreased significantly. These data suggest that treatment with VIP inhibits gastric cancer.