The Study Of Inhibitory Effect And Mechanism Of Il-18 On The Growth And Metastasis In Mice Bearing Lewis Lung Carcinoma

Objective To investigate the inhibitory effect and mechanism of IL-18 on the growth and metastasis in mice bearing Lewis lung carcinoma.Methods 24 C57BL/6 mice were randomly divided into three equal groups: group A (IL-18 injection group, n=8); group B (Lewis lung cancer model, n=8); group C (normal control group, n=8). The Lewis lung cancer cells were cultured and implanted subcutaneously into the group A and group B, IL-18 and NS were given to group A and B respectively by intraperitoneal injection on 7th day (once every day, 7 times altogether). All the animals health status were observed, the volume and weight of subcutaneous tumors were measured, and the lung metastasis were detdcted by iron hematoxylin staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect the Th1/Th2 cytokines; TUNEL was used to assess apoptotic index of tumor cells in the xenografts; The Ki-67, the vascular endothelial growth factor A (VEGF-A), vascular endothelial growth factor C (VEGF-C), microvessel density (MVD) and lymphatic microvessel density (LVD) in tumor mass were measured by imuunohistochemistry staining (IHCS).Results IL-18 could effectively inhibit the growth of xenografts with 75% of inhibition rate while had no obvious effect on the health situation of animals. There was a significant difference in regard to the tubercle number of lung metastasis between the Group A and Group B (P<0.01), and the inhibition rate of lung metastasis was 61%. The concentration of IFN-γin group A and C were significantly higher than those in group B(P<0.05), and the concentration of IL-4 in group A and C were significantly lower than those in group B (P<0.05), but there was not significant difference between group A and C, no change of the level of IFN-γand IL-4 in the two groups (P>0.05); The tumor cell apoptosis index in group A was significantly higher than this in the group B, the difference was statistically significant (P<0.01); The expression level of Ki-67, VEGF-A, VEGF-C and MVD in Group A were significantly lower than those of Group B (P<0.01 or P<0.05), but there was no significant difference in microlymphatic counts between two groups (P>0.05).Conclusions IL-18 has therapeutic effect on the tumor growth and metastasis, and may be mediated via regulating Th1/Th2 balance in the C57BL/6 mice Lewis lung cancer model and enhancing the antitumor immunity of the host, cutting down tumor cell proliferation, promoting tumor cell apoptosis, inhibiting angiogenesis and lymphangiogenesis by downregulating the expression level of VEGF-A and VEGF-C.