强力霉素与碘油栓塞对兔VX2肝种植瘤VEGF、MMP-2表达的影响

Transcatheter arterial embolization with doxycycline and lipiodol down-regulates VEGF and MMP-2 expression in implanted hepatic VX2 tumors in rabbits

目的:观察经肝动脉强力霉素与碘油栓塞对兔VX2肝种植瘤生长、血管内皮生长因子(VEGF)及基质金属蛋白酶-2(MMP-2)表达的影响.方法:32只日本大耳白兔肝VX2瘤种植后2wk,随机分为4组:生理盐水组(A组)、碘化油栓塞组(B组)、阿霉素+碘化油组(C组)及强力霉素+碘化油组(D组).治疗1wk后,采用CT检测肿瘤大小,计算肿瘤的生长率,病理观察肿瘤坏死率,免疫组织化学方法测定瘤区的VEGF及MMP-2表达强度,免疫组织化学分析采用计算机图像分析系统.结果:治疗1wk后,各栓塞治疗组肿瘤生长受到明显抑制(136.4%±42.8%,125.8%±30.8%,116.7%±25.2%vs325.3%±75.0%,均P<0.05),组间差异无统计学意义(P>0.05);D组肿瘤坏死率大于B、C组(84.5%±5.2%vs67.3%±8.5%,71.4%±7.6%,均P<0.05).B、C组残余肿瘤区的VEGF表达升高,高于A组(0.164±0.021,0.162±0.021vs0.141±0.018,均P<0.05);B、C组残留区MMP-2表达强度与A组相比统计学无显著性意义.D组肿瘤残留区的VEGF及MMP-2表达与A组相比均减弱(0.121±0.019vs0.141±0.018;0.135±0.027vs0.158±0.016,均P<0.05),且VEGF与MMP-2表达强度之间存在正相关(P<0.05).结论:强力霉素与碘油栓塞可抑制肿瘤生长,增加肿瘤的坏死率,降低栓塞后残瘤的VEGF及MMP-2表达.

AIM：To investigate the effect of transcatheter arterial embolization with doxycycline and lipiodol on tumor growth and the expression of vascular endothelial growth factor（VEGF） and matrix metalloproteinases-2（MMP-2） in hepatic tumors.METHODS：VX2 carcinoma was implanted in the left lobe of the liver of rabbits.Two weeks later,32 tumor-bearing rabbits were randomly and equally divided into four groups：normal saline group,lipiodol group,adriamycin plus lipiodol group,and doxycycline plus lipiodol group.Tumor size was measured by CT to calculate tumor growth rate.Tumor necrosis rate was assessed pathologically.The expression levels of VEGF and MMP-2 in tumors were examined by immunohistochemistry.The staining intensity of VEGF and MMP-2 was evaluated with a computer-assisted image analyzer.RESULTS：One week after treatment,the growth of tumors was significantly suppressed in the lipiodol group,adriamycin plus lipiodol group,and doxycycline plus lipiodol group compared with the normal saline group（136.4% ± 42.8%,125.8% ± 30.8%,116.7% ± 25.2% vs 325.3% ± 75.0%,all P〈0.05）.Tumor necrosis rate was significantly higher in the doxycycline plus lipiodol group than in the lipiodol group and adriamycin plus lipiodol group（84.5% ± 5.2% vs 67.3% ± 8.5%,71.4% ± 7.6%,both P〈0.05）.The expression of VEGF was significantly up-regulated in the lipiodol group and adriamycin plus lipiodol group compared with the normal saline group（0.164 ± 0.021,0.162 ± 0.021 vs 0.141 ± 0.018,both P〈0.05）.MMP-2 was slightly up-regulated in the lipiodol group and adriamycin plus lipiodol group compared with the normal saline group（both P〈0.05）.The expression levels of VEGF and MMP-2 were signifi cantly lower in the doxycycline plus lipiodol group than in the normal saline group（0.121 ± 0.019 vs 0.141 ± 0.018;0.135 ± 0.027 vs 0.158 ± 0.016,both P〈0.05）.There is a positive correlation between the expression of MMP-2 and VEGF.CONCLUSION：Trancatheter arterial embolization with doxycycline and lipiodol can suppress tumor growth,increase tumor necrosis,and decrease VEGF and MMP-2 expression in implanted hepatic VX2 tumors in rabbits.