Interleukin-18 Suppresses Angiogenesis and Lymphangiogenesis in Implanted Lewis Lung Cancer
Abstract
Objective:To investigate the effects of interleukin-18 (IL-18) on implanted Lewis lung cancer in suppressing angiogenesis and lymphangiogenesis.
Methods: One week after hypodermic inoculation of Lewis cells, sixteen tumor-bearing syngeneic mice were randomly divided into two groups. The mice in the treatment group (group A) were intraperitoneally injected with the IL-18 and in the control group (group B) were intraperitoneally injected with normal saline for 7 days. The mice were killed on day 19. The morphology of the tumors was studied, the growth curve was described and the tumor inhibition rate was calculated. The numbers of metastasized pulmonary colonies were calculated using hematoxylin-eosin (HE) staining. The vascular endothelial growth factor A (VEGF-A), vascular endothelial growth factor C (VEGF-C), microvessel density (MVD) and lymphatic microvessel density (LMVD) in tumor mass were measured by immunohistochemistry staining (IHCS).
Results: In the group A, the tumor volume, tumor weigh, lung metastatic nodules, expression of VEGF-A and VEGF-C, MVD were all decreased significantly (P<0.01 or P<0.05). The tumor inhibition rate was 75% and the inhibition rate of lung metastatic nodules was 61%. The LMVD in group A was also lower than group B, but without significant difference (P>0.05).
Conclusion: IL-18 could suppress the tumor growth and metastasis of implanted Lewis lung cancer by way of down-regulating VEGF-A and VEGF-C expression, suppressing angiogenesis and lymphangiogenesis.
Methods: One week after hypodermic inoculation of Lewis cells, sixteen tumor-bearing syngeneic mice were randomly divided into two groups. The mice in the treatment group (group A) were intraperitoneally injected with the IL-18 and in the control group (group B) were intraperitoneally injected with normal saline for 7 days. The mice were killed on day 19. The morphology of the tumors was studied, the growth curve was described and the tumor inhibition rate was calculated. The numbers of metastasized pulmonary colonies were calculated using hematoxylin-eosin (HE) staining. The vascular endothelial growth factor A (VEGF-A), vascular endothelial growth factor C (VEGF-C), microvessel density (MVD) and lymphatic microvessel density (LMVD) in tumor mass were measured by immunohistochemistry staining (IHCS).
Results: In the group A, the tumor volume, tumor weigh, lung metastatic nodules, expression of VEGF-A and VEGF-C, MVD were all decreased significantly (P<0.01 or P<0.05). The tumor inhibition rate was 75% and the inhibition rate of lung metastatic nodules was 61%. The LMVD in group A was also lower than group B, but without significant difference (P>0.05).
Conclusion: IL-18 could suppress the tumor growth and metastasis of implanted Lewis lung cancer by way of down-regulating VEGF-A and VEGF-C expression, suppressing angiogenesis and lymphangiogenesis.