强力霉素与碘油栓塞对兔VX2肝种植瘤转移和MMP-2、MMP-9表达的影响

Effects of doxycycline and lipiodol on metastasis and MMP-2/MMP-9 expression of VX2 hepatic xenografts 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、转移、基质金属蛋白酶2(MMP-2)及MMP-9表达的影响。方法 32只日本大耳白兔随机均分为4组,肿瘤种植后2周,经肝动脉插管分别给予不同处理:生理盐水组(A组)、碘化油组(B组)、阿霉素+碘化油(C组)及强力霉素+碘化油组(D组)。肿瘤种植后5周处死取肝脏及双肺标本,计算肝脏肿瘤体积及坏死率,并观察双肺转移瘤情况,免疫组化方法测定瘤区的MMP-2和MMP-9表达强度。结果肿瘤种植5周后,D组肿瘤体积小于与其他组(P<0.05)。D组双肺转移结节数目减少于其他各组(P<0.05),残存肿瘤区MMP-2及MMP-9表达均减低(P<0.05)。MMP-2与MMP-9表达强度与双肺转移瘤数量间存在正相关。结论强力霉素与碘油栓塞可降低残瘤MMP-2、MMP-9表达,在一定程度上抑制肿瘤生长及转移。

Objective To observe the effects of doxycycline and lipiodol on the growth,metastasis of VX2 hepatic xenografts,matrix metalloproteinases-2（MMP-2） and MMP-9 expression in VX2-transplanted liver tumor in rabbits.Methods A total of 32 healthy Japanese white rabbits were randomly divided into four groups and then VX2 carcinoma was implanted into the liver.Two weeks later,a catheter was inserted into the hepatic artery of rabbit and infusion was performed via the hepatic artery using normal saline（group A）,lipiodol（group B）,adriamycin plus lipiodol（group C）,and doxycycine plus lipiodol（group D）.Five weeks after tumor inoculation,all ribbits were sacrificed and the xenografts and lungs were taken out for measuring the volume and necrotic area of the implanted tumor,observing pulmonary metastases and detecting the expressions of MMP-2 and MMP-9 by immunohistochemistry.Results Compared to groups of A,B and C,the volume of xenografts was smaller,the number of metastatic tumor in the lungs was less,and the expressions of MMP-2 and MMP-9 in the residual tumors were lower in group D（P〈0.05）.The expressions of MMP-2 and MMP-9 were positively correlated with the numbers of pulmonary metastasis.ConclusionDoxycycline and lipiodol can decrease the expressions of MMP-2 and MMP-9 in the residual tumors after embolization,and inhibit in some degree the growth and metastasis of VX2-transplanted liver tumor in rabbits.