Sun Bao-cun, Zhang Shi-wu, Qi Li-sha, Zhang Dann-fang, Guo Hua, Zhao Xiu-lan
Department of Pathology, Tumor Hospital, Tianjin Medical University, China.
Zhonghua Zhong Liu Za Zhi. 2007 Jul;29(7):500-4.
To investigate the effects of endostatin and doxycycline on microcirculation patterns in melanoma and their molecular mechanisms.
To establish mouse B16 melanoma model by subcutaneous injection of B16 melanoma cell suspension. The mice were divided into 3 experimental groups and 1 control group. To treat the mice in the 3 experimental groups with endostatin, doxycycline, endostatin and doxycycline, respectively, and the control group without any treatment. The tumor volume was measured and recorded to make comparison of their growth rate. To assess the expression of MMP-2, MMP-9 and TIMP-2 by immunohistochemical staining. The three microcirculation patterns of endothelium-dependent vessels, mosaic vessels and vasculogenic mimicry were counted. The activity of MMP-2, MMP-9 between different groups was examined by gelatin zymography.
Tumor growth in the three experimental groups was statistically significantly slower than that in the control group. The expression of MMP-2, MMP-9 and TIMP-2 in each treated group was significantly different with that in the control group. The amount of three microcirculation patterns in three experimental groups was less than that of the control group, and the amount of MV and VM in each experimental group was significantly less than that in the control group. By gelatin zymography, the enzyme activity of MMP-9, actived-MMP-2 and MMP-2/proMMP-2 in ES, DOX and ES + DOX group was lower than that in the control group, but the enzyme activity of pro-MMP-2 among the four groups was not significantly different.
The combined use of doxycycline and endostatin in melanoma can inhibit the expression of MMPs, influencing the formation of different microcirculation patterns in melanoma.
研究内皮抑素和强力霉素对黑色素瘤微循环模式的影响及其分子机制。
通过皮下注射B16黑色素瘤细胞悬液建立小鼠B16黑色素瘤模型。将小鼠分为3个实验组和1个对照组。分别用内皮抑素、强力霉素、内皮抑素与强力霉素联合处理3个实验组的小鼠，对照组不做任何处理。测量并记录肿瘤体积，比较其生长速率。通过免疫组织化学染色评估基质金属蛋白酶-2（MMP-2）、基质金属蛋白酶-9（MMP-9）和金属蛋白酶组织抑制因子-2（TIMP-2）的表达。计数内皮依赖性血管、镶嵌血管和血管生成拟态这三种微循环模式。通过明胶酶谱法检测不同组之间MMP-2、MMP-9的活性。
三个实验组的肿瘤生长在统计学上显著慢于对照组。各处理组中MMP-2、MMP-9和TIMP-2的表达与对照组有显著差异。三个实验组中三种微循环模式的数量均少于对照组，且各实验组中镶嵌血管（MV）和血管生成拟态（VM）的数量均显著少于对照组。通过明胶酶谱法检测，内皮抑素组、强力霉素组和内皮抑素+强力霉素组中MMP-9、活化型MMP-2和MMP-2/前MMP-2的酶活性低于对照组，但四组之间前MMP-2的酶活性无显著差异。
强力霉素与内皮抑素联合应用于黑色素瘤可抑制基质金属蛋白酶的表达，影响黑色素瘤中不同微循环模式的形成。
