Antitumor Effect of Docetaxel-Loaded Lipid Microbubbles Combined With Ultrasound-Targeted Microbubble Activation on VX2 Rabbit Liver Tumors
Antitumor Effect of Docetaxel-Loaded Lipid Microbubbles Combined With Ultrasound-Targeted Microbubble Activation on VX2 Rabbit Liver Tumors
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DOI：
10.7863/jum.2010.29.1.61
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发表时间：
2010-01-01
影响因子：
2.3
通讯作者：
Zhang, Yong
中科院分区：
文献类型：
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作者：
Kang, Juan;Wu, Xiaoling;Zhang, Yong
Objective.探讨紫杉醇脂质微泡联合超声靶向微泡激活（UTMA）对兔VX 2肝癌的抑制作用。方法.采用机械振动法制备多西他赛脂质微泡。将90只兔建立VX 2肝癌模型，随机分为6组，分别为对照组、紫杉醇单用组、紫杉醇单用组、紫杉醇联合超声组、紫杉醇单用组、紫杉醇联合超声组、紫杉醇联合超声组（DOC+MB/US）。计算肿瘤体积和肿瘤生长抑制率（IR）并进行比较。末端脱氧尿苷缺口末端标记法检测细胞凋亡。免疫组化检测肿瘤细胞核抗原和基质金属蛋白酶2（MMP 2）蛋白表达。原位杂交组织化学法检测Caspase 3和MMP 2 mRNA的表达。比较各组动物的肿瘤转移率和生存时间。结果DOC+MB/US组的IR和凋亡指数最高，增殖标记指数最低。DOC + MB/US组基质金属蛋白酶2蛋白和mRNA表达最低，caspase 3 mRNA表达最高。DOC+MB/US组的广泛转移率最低，DOC+MB/US组的动物存活时间最长。结论.多西他赛脂质微泡联合UTMA可通过延缓增殖、促进凋亡抑制VX 2兔肝癌的生长，为肝癌的靶向化疗提供了新的策略。
Objective. The purpose of the study was to explore the antitumor effect of docetaxel-loaded lipid microbubbles combined with ultrasound-targeted microbubble activation (UTMA) on VX2 rabbit liver tumors. Methods. Docetaxel-loaded lipid microbubbles were made by a mechanical vibration technique. VX2 liver tumor models were established in 90 rabbits, which were randomly divided into 6 groups, including control, docetaxal-loaded lipid microbubbles alone, docetaxal alone, docetaxal combined with ultrasound, pure lipid microbubbles combined with ultrasound, and docetaxel-loaded lipid microbubbles combined with ultrasound (DOC+MB/US). The tumor volume and inhibition rate (IR) of tumor growth were calculated and compared. Apoptosis was detected by terminal deoxyuridine nick end labeling. Proliferating cell nuclear antigen and matrix metalloproteinase 2 (MMP2) protein expression was detected by immunohistochemistry. Caspase 3 and MMP2 messenger RNA (mRNA) expression was detected by in situ hybridization histochemistry. The tumor metastasis rate and survival time of the animals were compared. Results. The IR and apoptotic index of the DOC+MB/US group were the highest among all groups, and the proliferating labeling index was the lowest. Matrix metalloproteinase 2 protein and mRNA expression in the DOC+MB/US group was the lowest among all groups, and caspase 3 mRNA expression in the DOC+MB/US group was the highest. The extensive metastasis rate in the DOC+MB/US group was the lowest, and the survival time of the animals in the DOC+MB/US group was the longest. Conclusions. Docetaxel-loaded lipid microbubbles combined with UTMA could inhibit the growth of VX2 rabbit liver tumors by deferring proliferation and promoting apoptosis, which may provide a novel targeted strategy for chemotherapy of liver carcinoma.