The Inhibitory Effect Of Different Doses Of Celecoxib On Lewis Lung Tumor Lymphangiogenesis

Objective:To observe the effect of celecoxib,a cyclooxygenase-2 inhibitor,on tumor growth,COX-2,VEGF-C expression and lymphangiogenesis in Lewi Lung Carcinoma homograft in C57BL/6 mice and explore the possible role of different doses of Celecoxib on Lewis lung tumor lymphangiogenesis mechanism.Methods:Lewi Lung Carcinoma cell lines were seeded in C57BL/6 left groin subcutaneous to establish homograft models.These models were randomly divided into four groups:control group,low-dose,medium-dose,and high dose group.Then we observed the tumor-bearing survival statuses and tumor volume changes of the mice.Transplanted tumor tissues were collected after 42 days and we made a detection of COX-2,VEGF-C expression and lymphatic microvessel density by immunohistochemical staining method.Results:Low-dose group,medium-dose group and high-dose group of Celecoxib inhibition rates were 13.3%,46.8%and 56.3%,respectively.Compared with the control group.There were significant statistacally differences in the inhibitory effect on tumors of high and medium-dose groups(P<0.05),however no difference could be seen in low-dose group(P>0.05).Immunohistochemical staining showed that celecoxib with medium and high-dose lowered the expressions of COX-2,VEGF-C and lymphatic microvessel density(LMVD).And compared with the control group,there were significant differences(P<0.05).Though expressive levels decreased slightly,there were no significant differences between Low-dose group and control group(P>0.05).The degree of inhibition was dose-related.Conclusion:Celecoxib inhibits the growth of Lewis lung tumor and lymph node metastasis by reducing expressions of COX-2 and VEGF-C and inhibiting lymphangiogenesis which is related to dosage.