目的探讨金属蛋白酶抑制剂（ＴＩＭＰ２）基因转染后胃癌细胞的体内外侵袭能力的改变及胶原与胶原酶的变化规律．方法将人全长ＴＩＭＰ２ｃＤＮＡ基因构建于改构的逆转录病毒载体ｐＬＭＴ，经基因转染法导入人胃癌细胞系ＳＧＣ７９０１，Ｇ４１８筛选获阳性细胞．利用裸鼠肾包膜下移植模型，采用免疫组化和原位杂交方法，观察肿瘤发展过程中的不同时期ＴＩＭＰｓ／ＭＭＰｓ（基质金属蛋白酶）ｍＲＮＡ，Ⅳ型胶原表达的情况．结果随着肿瘤移植后时间的延长，瘤细胞侵袭基底膜处Ⅳ型胶原缺失，瘤巢周围ＭＭＰｓ含量丰富．通过体外实验，观察到ＳＧＣ７９０１Ｔ２细胞ＴＩＭＰ２ｍＲＮＡ及蛋白活性均高于母系ＳＧＣ７９０１细胞，ＴＩＭＰ２可抑制基质金属蛋白酶的活性，减弱肿瘤细胞的侵袭体内外移动速度．结论ＭＭＰｓ的高表达是肿瘤细胞侵袭的关键因素，而ＴＩＭＰ２基因是恶性肿瘤侵袭和转移的负调控因子． Objective To investigate the changes of invasiveness of gastric cancer cells in vitro and in vivo and the changes of collagen and collagenase after transfection of TIMP2 gene. Methods The human full-length TIMP 2 cDNA gene was constructed in retrofit retroviral vector pL MT, gene transfected into human gastric cancer cell line SGC 7901, G418 screening positive cells. Using subcutaneous renal capsule transplantation model in nude mice, immunohistochemistry and in situ hybridization were used to observe the expression of TIMPs / MMPs mRNA and type Ⅳ collagen in different stages of tumor development. Results With the extension of time after tumor transplantation, type IV collagen was absent in the basement membrane of tumor cells and rich in MMPs around tumor nests. Through in vitro experiments, it was observed that the activity of TIMP-2 mRNA and protein in SGC7901T2 cells was higher than that in maternal SGC7901 cells. TIMP2 inhibited the activity of MMPs and decreased the invasion speed of tumor cells in vivo and in vitro. Conclusion The high expression of MMPs is the key factor of tumor cell invasion, and TIMP 2 gene is a negative regulator of invasion and metastasis of malignant tumor.