Effect of cisplatin on expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 and their correlations in Lewis lung cancer in mice

Abstract

Metastasis of lung cancer is the leading cause of disease progression and treatment failure. Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) are related to the metastasis of lung cancer via regulating the degradation of extracellular matrix. This study was to observe the impacts of cisplatin (DDP) on the expression of MMP-9 and TIMP-1 in Lewis lung cancer, and explore their correlations and roles in metastasis. Lewis lung cancer model was established in C57BL/6 mice. DDP group was given intraperitoneal DDP injection, and compared with normal control and tumor-bearing groups. The expression of MMP-9 and TIMP-1 were determined by ELISA in serum and detected by immunohistochemistry in tumor tissues. The inhibition rates of tumor growth and metastasis were 41.2% and 39.0% in DDP group, respectively. The positive rates of MMP-9 and TIMP-1 were 100% in tumor-bearing group, and their serum concentrations were significantly higher in tumor-bearing group than in normal control group (P<0.05). Serum concentrations of MMP-9 and TIMP-1, and positive rate of MMP-9 were all significantly lower in DDP group than in tumor-bearing group (P<0.05). Serum concentration of MMP-9 and positive rates of MMP-9 and TIMP-1 were positively correlated to tumor weight (r=0.665, 0.749 and 0.615, all P<0.05) and lung metastasis (r=0.668, 0.545 and 0.664, all P<0.05). MMP-9 expression was positively correlated to TIMP-1 expression both in serum and tumor (r=0.617 and 0.695, all P<0.05). The ratio of sMMP-9/TIMP-1 became a constant in normal distribution, with a mean of 1.72. Both MMP-9 and TIMP-1 are highly expressed in Lewis lung cancer, correlated to tumor invasion and metastasis. DDP may suppress tumor metastasis via down-regulating the expression of MMP-9 and TIMP-1 in serum and tumor.