携反义基质金属蛋白酶-2的重组腺病毒对肝癌生长的影响

目的探讨携带反义二型基质金属蛋白酶（MMP2）基因的重组腺病毒（Ad-MMP2^AS）对人肝癌细胞株（Bel-7402）体外侵袭性和人肝癌动物模型生长的抑制作用。方法用已构建的Ad-MMP2^AS感染人肝癌细胞株（Bel-7402），用侵袭小室模型检测Ad-MMP2^AS对Bel-7402细胞降解人工基底膜的抑制作用；用Western Blot和明胶酶谱检测Ad-MMP2^AS对Bel-7402细胞分泌MMP2的影响；用感染了Ad-MMP2^AS的Bel-7402细胞接种于裸鼠皮下，使其在裸鼠体内成瘤，以观察其成瘤能力；用Ad-MMP2^AS瘤内注射，以观察它对肝癌生长的抑制作用。结果Ad-MMP2^AS感染的Bel-7402细胞分泌MMP2被抑制、穿过人工基底膜Matrigel的Bel-7402细胞数下降52％、感染Ad-MMP2^AS的Bel-7402细胞的成瘤量下降4．3倍，Ad-MMP2^AS瘤内注射后瘤体生长减少63％。结论Ad-MMP2^AS能明显抑制肝癌的生长，对肝癌有治疗潜力。

Recombinant Adenovirus Vectors Carrying Antisense Matrix Metalloproteinase-2 Inhibits Hepatocellular Carcinoma Growth in vivo

Objective To investigate the inhibitory effect of a recombinant adenoviral vector carrying antisense matrix metalloproteinase-2(MMP2) on the growth of hepatocellular carcinoma(HCC) in vivo.Methods The recombinant adenoviral vector carrying antisense MMP2(Ad-MMP2~(AS))which had been constructed by us in readiness was used to infect the human HCC cell line(Bel-7402).Then the invasiveness of the Bel-7402 cells was assayed in Matrigel,and the production of MMP2 in the Bel-7402 cells was detected with Western blot analysis and Gelatin zymography.After the Ad-MMP2~(AS)-infected Bel-7402 cells being subcutaneously inoculated in nude mice,the production of tumors was under observation,and then Ad-MMP2~(AS) was injected intratumorally into the pre-existing tumors.Results Compared with PBS or Ad-CMV-infected cells,infection of Bel-7402 cells with Ad-MMP2~(AS) significantly reduced MMP2 enzyme activity,the invasiveness resulted in 52% reduction in Matrigel assays,and the tumor volume displayed a 4.3-fold reduction in nude mice.In addition,direct intratumoral injection of Ad-MMP2~(AS) into pre-existing tumors significantly impaired the further expansion of the tumor mass and resulted in a 63% reduction in tumor cell growth.Conclusion The recombinant adenovirus with antisense MMP2 can effectively inhibit the invasiveness and growth of Bel-7402 cells in vitro and in vivo,and has a therapeutic potential for HCC.