【摘要】 目的研究内皮抑素和多西环素对黑色素瘤生长及肿瘤细胞基质金属蛋白酶-9(MMP-9)、-2(MMP-2)及基质金属蛋白酶组织抑制因子(TIMP-2)表达水平的影响。方法C57/BL6小鼠57只,建立小鼠B16黑色素瘤动物模型,分多西环素组、多西环素加内皮抑素组,内皮抑素组和对照组4组,给予内皮抑素和多西环素处理,比较肿瘤的体积大小及生长速度,免疫组织化学染色检测肿瘤组织MMP-9、MMP-2及TIMP-2的表达。结果多西环素组、多西环素加内皮抑素组和内皮抑素组肿瘤均较对照组生长缓慢(F=4.32,P<0.05),其中多西环素组、多西环素加内皮抑素组和对照组之间肿瘤平均生长体积差异有统计学意义(t=2.40,t=2.58;P<0.05)。MMP-2、MMP-9和TIMP-2在各处理组的表达与在对照组的表达之间差异均有统计学意义(F=12.79,F=5.56,F=4.64;P<0.05)。结论多西环素和内皮抑素联合使用,影响肿瘤组织MMPs及其抑制剂的表达,明显抑制黑色素瘤生长和局部浸润转移。更多还原

【Abstract】 Objective To investigate the molecular mechanism of endostatin and doxycycline effect on melanoma growth. Methods A B16 melanoma mice model was established by intracutaneous injection of B16 cell suspension. The mice were treated with endostatin, doxycycline, endostatin and doxycycline respectively, the control group received no treatment. A time course study of tumor volume was performed to observe the antitumor effect. The expression of matrix metalloproteinase (MMP-9), MMP-2, TIMP-2 were examined by immunohistochemistry staining. Results Tumors in endostatin treatment group, doxycycline treatment group, endostatin and doxycycline treatment group grew slower than in the control group. The difference of the average tumor volume in the doxycycline group and control group, in the doxycycline with endostatin treatment group and control group were statistically different. The positive expression ratio of MMP-2,MMP-9,TIMP-2 in each treatment group were statistically different from their control groups(F=12.79,F=5.56,F=4.64;P<0.05).Conclusion Doxycycline and endostatin are able to inhibit the expression of MMPs and promote expression of TIMP, which ultimately inhibits the growth of B16 melonoma.更多还原