TIMP-3基因转染抑制人肺癌细胞系侵袭与转移的研究

目的探讨金属蛋白酶组织抑制因子３（ＴＩＭＰ３）对高转移性人肺巨细胞癌细胞系（ＢＥ１）恶性表型的影响。方法构建含全长人ＴＩＭＰ３ｃＤＮＡ的真核表达载体,用脂质体法转入ＢＥ１细胞。检测转染后ＢＥ１细胞的体外侵袭及裸鼠体内成瘤性及转移能力的变化。结果ＢＥ１细胞在转入ＴＩＭＰ３ｃＤＮＡ后表达ＴＩＭＰ３ｍＲＮＡ,与母系及空载体对照相比,体外侵袭力降低,在裸鼠体内成瘤率降低（对照组６／６只,实验组９／１２只）,成瘤潜伏期延长,转移至肺和淋巴结的能力降低（对照组分别为５／６只和６／６只;实验组分别为１／１２只和５／１２只）。结论特异性上调ＴＩＭＰ３基因的表达可在一定程度上逆转ＢＥ１细胞的恶性表型

The suppressing effect of TIMP-3 gene transfection on the invasion and metastasis of human lung carcinoma cells line

Objective The purpose of this study is to determine if increasing levels of tissue inhibitor of metalloproteinase 3 (TIMP 3) expression could suppress the malignant phenotype of human cancer cells. Methods The recombinant expression vector, which contains full length cDNA of human TIMP 3, was constructed and transfected into BE1 cell line by lipofectin technique. The invasive and spontaneous metastatic potential was examined. Results TIMP 3 mRNA expression in TIMP 3 gene transfected BE1 cells was upregulated as detected by Northern blot. The invasion of TIMP 3 gene transfected cells across matrigel coated filters was significantly decreased when compared with controls. Following subcutaneous injection into nude mice, the TIMP 3 transfected cells suppressed primary tumor growth, as characterized by reduced tumor incidence (9/12 vs 6/6), longer latency and reduced metastatic potential to the lungs (1/12 vs 5/6) and lymph nodes (5/12 vs 6/6). Conclusion The results suggest that upregulation of TIMP 3 expression in BE1 cells resulted in suppression of the invasive potential of BE1 cells in vitro as well as tumorigenic and metastatic potential in nude mice.