目的 探讨超声辐照携带促黄体生成素释放激素类似物(LHRHa)的靶向微泡能否增强顺铂(DDP )对人卵巢癌裸鼠腹腔移植瘤的抑制作用.方法 利用LHRH受体阳性的人卵巢癌耐药细胞A2780/DDP建立裸鼠腹腔移植瘤模型.将30只荷瘤鼠随机分成6组,即DDP+靶向微泡+超声组(Ⅰ),DDP+普通微泡+超声组(Ⅱ),DDP组(Ⅲ ),靶向微泡+超声组(Ⅳ),靶向微泡组(Ⅴ)和生理盐水对照组,Ⅰ～V组为实验组.处理结束后记录肿瘤个数,剖取瘤块称湿质量,计算抑瘤率;对肿瘤及主要脏器进行病理组织学检查;免疫组化SP法检测肿瘤组织中基质金属蛋白酶-9 (MMP-9)的表达.结果 各组的肿瘤个数、质量和MMP-9表达均有差异(P<0.01),其中,工组的抑瘤率最大,其肿瘤个数、质量和MMP-9表达均显著低于其他4个实验组(P<0.05)和对照组(P<0.01).结论 超声辐照LHRHa靶向微泡能显著增强DDP对卵巢癌移植瘤的抑制作用.%Objective To approach whether LHRHa-targeted microbubbles with ultrasound irradiation could enhance the inhibition of cisplatin (DDP) on human ovarian carcinoma transplanted intraperitoneally in nude mice. Methods The nude mouse models of intraperitoneal xenografts were established with human ovarian carcinoma cells A2780/DDP(DDP-resistant,LHRH receptor positive). Thirty tumor-bearing mice were randomly divided into six groups: group Ⅰ (DDP + targeted microbubbles + ultrasound), group Ⅱ ( DDP + common microbubbles + ultrasound),group Ⅲ (DDP),groupⅣ (targeted microbubbles+ ultrasound), group Ⅴ (targeted microbubbles) and the control group (normal saline). Group Ⅰ ～ Ⅴ were experimental groups. After the last treatment, all mice were sacrificed, and their tumors were immediately excised, counted and weighed. The tumor inhibition rate was calculated by tumor mass. The main organs and tumors were given histopathologic examinations. Expressions of matrix metalloproteinase-9 (MMP-9)in tumor tissues were detected by immunohistochemical staining with Streptavidin/Peroxidase(SP) method. Results The tumor number,mass and MMP-9 expression all varied among the groups(P＜0.01) ,and the tumor inhibition rate was the highest in group Ⅰ ,its tumor number, mass and MMP-9 expression were all significantly lower than those of the other four experimental groups(P＜0.05) and the control group(P＜0.01). Conclusions LHRHa-targeted microbubbles with ultrasound irradiation can significantly enhance the inhibition of DDP on xenografted ovarian carcinoma.
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