Li Chun-Jie, Sun Jian-Li, Jiang Wei-Jie, Liu Ling-Shuang, Sun Xi-Yuan, Fan Guo-Zhong
Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
Ai Zheng. 2009 Jul;28(7):685-90. doi: 10.5732/cjc.009.10025.
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.
肺癌转移是疾病进展和治疗失败的主要原因。基质金属蛋白酶-9（MMP-9）和金属蛋白酶组织抑制剂-1（TIMP-1）通过调节细胞外基质的降解与肺癌转移相关。本研究旨在观察顺铂（DDP）对Lewis肺癌中MMP-9和TIMP-1表达的影响，并探讨它们在转移中的相关性及作用。
在C57BL/6小鼠中建立Lewis肺癌模型。DDP组腹腔注射DDP，并与正常对照组和荷瘤组进行比较。采用酶联免疫吸附测定法（ELISA）检测血清中MMP-9和TIMP-1的表达，采用免疫组织化学法检测肿瘤组织中MMP-9和TIMP-1的表达。
DDP组肿瘤生长和转移的抑制率分别为41.2%和39.0%。荷瘤组MMP-9和TIMP-1的阳性率均为100%，其血清浓度荷瘤组明显高于正常对照组（P<0.05）。DDP组血清中MMP-9和TIMP-1的浓度以及MMP-9的阳性率均明显低于荷瘤组（P<0.05）。血清中MMP-9的浓度、MMP-9和TIMP-1的阳性率与肿瘤重量（r=0.665、0.749和0.615，均P<0.05）及肺转移（r=0.668、0.545和0.664，均P<0.05）呈正相关。血清和肿瘤中MMP-9的表达与TIMP-1的表达均呈正相关（r=0.617和0.695，均P<0.05）。sMMP-9/TIMP-1的比值呈正态分布且为常数，平均值为1.72。
MMP-9和TIMP-1在Lewis肺癌中均高表达，与肿瘤侵袭和转移相关。DDP可能通过下调血清和肿瘤中MMP-9和TIMP-1的表达来抑制肿瘤转移。
