摘要
目的观察多西环素对小鼠恶性黑色素瘤模型MMP-2、MMP-9表达和活性的作用。方法C57／BL小鼠47只建立黑色素瘤模型，随机分为给药组和对照组。给药组每日腹腔注射盐酸多西环素，对照组给予等量生理盐水。7d后处死给药组和对照组小鼠各10只。继续给药14d后处死剩余小鼠，比较两个时间点多西环素对MMP-2、MMP-9、VEGF表达的影响。并用检测MMP-9、MMP-2酶原、活性MMP-2的活性变化。结果多西环素给药7d抑瘤率为52．36％，给药14d抑瘤率为35．63％。给药组的MMP-2、MMP-9表达均低于对照组，而VEGF的表达高于对照组。给药组的MMP-9和活性MMP-2的条带酶解量以及活性MMP-2与MMP-2酶原比值均低于对照组，但两组间MMP-2酶原条带酶解量差异无统计学意义。结论多西环素可以抑制恶性黑色素瘤小鼠移植瘤的生长，其作用机制可能和抑制MMP-2、MMP-9的表达和活性有关。
Objective To examine the inhibitory effects of doxycycline on the expression and activity of MMP-2 and MMP-9 in mouse melanoma transplanted tumor model. Methods Forty-seven C57 mice were randomly divided into doxycycline treatment group and control group. The melanoma transplanted model was established by subcutaneous injection of B16 cells suspending liquid into mice. Mice in treatment group were injected with doxycycline and those in control group with physiological saline solution everyday when tumor could be touched. Seven days later, 10 mice in each group were killed, and 14 days later all other mice were killed. The expression level of MMP-2, MMP-9 and VEGF was detected by IHC. The activity of MMP-2 and MMP-9 between different groups was examined by gelatin zymography. Results The inhibition rate （IR） was 52.36% after treatment for 7 days,but the IR was decreased to 35.63% after treatment for 14 days. After treatment for 7 days, the expression level of MMP-2 and MMP-9 in treatment group was lower than in control group （P 〈 0.01, P 〈 0.05 ） and that of VEGF in treatment group was higher than in control group （P 〈0.05）. After treatment for 14 days,the expression level of MMP-2 and MMP-9 in treatment group was lower than in control group （P 〈0.01 ,P 〈0.01 ） and the expression level of VEGF in treatment group was higher than in control group （ P 〈 0.05 ）. By gelatin zymography, the enzyme activity of MMP-9,actived-MMP-2 and MMP-2/pro-MMP-2 in treatment group were lower than in control group （ P 〈 0.01 ）, but the enzyme activity of pro-MMP-2 between two groups had no significant difference （P 〉 0.05 ）. Conclusion Doxycycline could suppress the growth of malignant melanoma in mouse transplanted tumor model, which may be associated with the inhibitory effects of doxycycline on the expression and activity of MMP-2 and MMP-9.
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2008年第11期1427-1429,共3页
Chinese Journal of Experimental Surgery
基金
国家自然科学基金资助项目（30370554）
关键词
多西环素
黑色素瘤
基质金属蛋白酶
Doxycycline
Malignant Melanoma
Matrix metalloproteinases
