基质金属蛋白酶抑制剂Marimastat抑制胃癌生长和转移的作用

目的:观察基质金属蛋白酶(MMP)抑制剂Marimastat对人胃癌在裸鼠体内生长和转移的抑制作用。方法:人胃腺癌细胞株SGC-7901完整组织块裸鼠原位种植,建立类似于临床的胃癌转移模型。移植7 d后,治疗组开始腹腔内注射Mari-mastat,隔天1次,剂量为10、30、60 mg/kg,每个剂量组13只裸鼠,对照组13只裸鼠给予相同量的生理盐水,8周后处死动物,测量原位肿瘤大小,计算抑瘤率,免疫组织化学法检测肿瘤微血管密度(MVD)、MMP-9的表达率,并观察肿瘤转移情况。结果:对照组和治疗组Marimastat剂量为10、30、60mg/kg时,原位肿瘤质量分别为(1.63±0.53)、(0.71±0.28)、(0.33±0.17)、(0.14±0.09)g;抑瘤率分别为0、56.4％、79.8％、91.4％;MVD分别为(1.36±4.56)、(8.74±2.22)、(3.25±1.29)、(0.92±0.76);MMP-9的表达率分别为81.8％、38.5％、23.1％、0;腹膜转移率分别为81.8％、30.8％、15.4％、0;肝脏转移率分别为90.9％、38.5％、23.1％、0。治疗组与对照组相比,胃癌的生长和转移受到明显抑制(P<0.05),且与Marimastat的剂量呈正相关。结论:Marimastat对体内胃癌的生长及转移均有抑制作用。

Inhibitory effect of matrix metalloproteinase Marimastat on growth and metastasis of human gastric cancer in nude mice

[ABSTRACT] Objective:To investigate the effects of matrix metalloproteinase(MMP) inhibitor Marimastat on the growth and metastasis of human gastric cancer in nude mice. Methods :Metastatic model simulating human gastric cancer was established by orthotopic implantation of histologically intact human tumor tissue into gastric wall of nude mice. Marimastat was injected into the peritoneal cavity of 13 mice in treated group at doses of Oi 10, 30, 60 mg/kg every other day for 8 weeks. Meanwhile,the same dose of normal salines were injected into 13 mice in control group. Nine weeks after implantation, the mice were sacrificed and the tumor weight, inhibition rates, microvessel density (MVD) ,MMP expression, tumor metastasis were all evaluated. Results:Compared with the control group, tumor growth was significantly inhibited in Marimastat-treated group with inhibition rates being 0,56. 4% , 79. 8% , 91. 4% in control group and at the doses of 10,30, 60 mg/kg, respectively. Expression rates of MMP-9C90. 9% ,38. 5% , 23. 1 % ,0) and the microvessel density [(15. 36 ?. 56), (8. 74 ?. 22), (3. 25?. 29), (0. 92?. 76)] decreased significantly in the treated mice. Tumor metastasis to the liver and peritoneum was also significantly inhibited by Marimastat in a dose-dependent manner. The growth and metastasis of human gastric cancer implanted in nude mice were significantly inhibited in treated group than those in control group (F<0. 05). Conclusion: Marimastat has strong inhibitory effects -on growth and metastasis of human gastric cancer in nude mice.