金属蛋白酶MMP-9表达与人黑色素瘤细胞系转移表型的相关性

A study on the correlation between the expression of matrix metalloproteinase 9 and the metastatic phenotype in human melanoma cells

目的 :探讨金属蛋白酶MMP 9与肿瘤转移的相关性。方法 :利用基因重组技术构建反义MMP 9cDNA真核表达载体 ,用脂质体法转染MMP 9高表达的转移性人黑色素瘤细胞株WM 45 1,检测转染后细胞MMP 9表达水平的改变以及体外生长、侵袭、裸鼠体内成瘤及自发转移能力的变化。结果 :转染细胞MMP 9的表达及活性明显下降 ,同时MMP 2的表达也受到一定抑制 ,细胞生长速度、体外侵袭能力及裸鼠体内成瘤性及自发转移能力均受到一定程度抑制。结论 :通过反义RNA技术下调MMP 9的表达 ,可使人黑色素细胞转移能力受到一定程度的抑制 ,说明MMP

Objective: To investigate the correlation between MMP 9 and tumor metastasis. Methods: A mammalian expression vector containing antisense cDNA of MMP 9 was constructed and transfected into a metastatic human melanoma cell line WM451 which had a high MMP 9 expression level. In vitro and in vivo tests such as MTT [3 (4,5 dimethylthiazol zyl) 2,5 diphenyl tetrazolium bromide] method, zymography as well as xenografting in nude mice experiments were used to analyse expression of MMPs and in vitro and in vivo behaviors of tumor cells before and after gene transfection. Results: After transfection the expression and activity of MMP 9 decreased significantly. The production of MMP 2 was also suppressed. The capacity of in vitro growth, invasion through Matrigel, tumorigenecity as well as spontaneous metastasis in nude mice was reduced to some extent. Conclusion: The decrease of MMP 9 expression in human melanoma cell line by MMP 9 antisense RNA could inhibit its metastatic phenotype and demonstrated that MMP 9 might play a central role in metastasis.