Effect and mechanism of antimicrobial peptide cathelicidin secreted by tumor associated macrophage on the growth of colorectal cancer in mice / 中华肿瘤杂志

ABSTRACT

Objective@#To investigate the effect and mechanism of the antibacterial peptide cathelicidin secreted by tumor associated macrophages on the growth of colorectal cancer in mice.@*Methods@#Azoxymethane (AOM)/ dextran sodium sulfate (DSS) method was used to establish a mouse model of colitis associated colon cancer. To induce tumor formation, cathelicidin antibody, IgG antibody (positive control) or PBS (negative control) was respectively injected into mice once every 3 days and lasted one month. Then the pictures of mice colon were taken, and the numbers of tumor were counted and evaluated. Expressions of cathelicidin in tumor associated macrophages isolated from tumor and adjacent normal tissues of mice were examined by quantitative RT-PCR (qRT-PCR) and Western blot. Expressions of the tumor proliferating antigen Ki-67, macrophage marker CD68 and cathelicidin in tumor and non-tumor tissues were determined by immunohistochemistry analysis. Apoptosis of cells from tumor tissues was analyzed by using TdT-mediated dUTP nick-end labeling (TUNEL).@*Results@#In colon tumor tissues, cathlicidin strongly expressed in inflammatory cells (macrophages), but weakly expressed in tumor cells. The tumor number and size in mice injected with cathelicidin neutralizing antibody were 4.50±1.18 and (1.74±0.18) mm, respectively, significantly lower than 13.88±1.98 and (3.74±0.38) mm of mice injected with PBS (t=4.07, t=4.72; P< 0.01) and 15.25±1.82 and (3.40±0.36) mm of mice injected with IgG antibody (t=4.96, t=4.08; P<0.01). The Ki-67 positive rate of cells in tumor tissues of mice injected with cathelicidin neutralizing antibody was (28.20±3.44) %, significantly lower than (68.20±3.51) % of mice injected with PBS (t=8.135, P<0.01) and (69.20±3.41) % of mice injected with IgG antibody (t=8.461, P<0.01). Immunohistochemistry analyses showed that the expression of CD68 in tumor tissues of mice injected with cathelicidin antibody was significantly lower than that of mice injected with IgG antibody or PBS. TUNEL result showed that treatment with cathelicidin neutralizing antibody had negligible effect on the apoptosis of tumor cells.@*Conclusions@#Cathelicidin secreted by tumor associated macrophages can promote the growth of colorectal cancer in mice, and neutralizing cathelicidin activity can inhibit the growth and proliferation of colorectal cancer. Cathelicidin mediated promotion of colon cancer proliferation may mainly be exerted by recruiting inflammatory cells such as macrophages into the tumor microenvironment.