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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Li
Chun-Jie
CJ
Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China. lichunjie1997@hotmail.com
Sun
Jian-Li
JL
Jiang
Wei-Jie
WJ
Liu
Ling-Shuang
LS
Sun
Xi-Yuan
XY
Fan
Guo-Zhong
GZ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018827:Carcinoma, Lewis Lung / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D002945:Cisplatin / Q000494:pharmacology*; D015536:Down-Regulation; D005260:Female; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood / Q000378:metabolism*; D047368:Tumor Burden / Q000187:drug effects
D000970:Antineoplastic Agents; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9; D002945:Cisplatin