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载多西紫杉醇 PLGA 微球化疗可减少人肝癌异种移植瘤血管生成。

Chemotherapy with PLGA microspheres containing docetaxel decreases angiogenesis in human hepatoma xenograft.

机构信息

Department of Ultrasound, Affiliated Union Hospital, Fujian Medical University, 350001 Fuzhou, Fujian, China.

出版信息

Med Oncol. 2012 Mar;29(1):62-9. doi: 10.1007/s12032-010-9762-2. Epub 2010 Dec 7.

Abstract

To investigate the antiangiogenic effect of sustained-release poly (lactic-co-glycolic acid) microspheres containing docetaxel (PMCD) in human hepatoma xenograft. PMCD were prepared by solvent evaporation method with an encapsulation efficiency of 98.7% and a release period of about 3 weeks in vitro. PMCD were intratumorally injected once for mice bearing a human hepatocellular carcinoma. On day 21 post-treatment, the inhibition rate of tumor growth was 72.7% in the high-dose group, indicating a significant antitumor activity. Meanwhile, excellent antiangiogenic effect was observed based on the contrast-enhanced ultrasonography as well as microvessel density determination. Additionally, the real-time fluorescence quantitative PCR revealed that the expressions of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and angiopoietin-2 (Ang2) genes were down-regulated significantly. Interstitial chemotherapy using PMCD was highly effective and safe for the treatment of the human hepatoma xenograft and that decreasing angiogenesis could be one of the most important mechanisms involved in the antitumor activity.

摘要

研究载多西紫杉醇聚乳酸-羟基乙酸共聚物微球(PMCD)的抗血管生成作用对人肝癌异种移植的影响。PMCD 采用溶剂蒸发法制备,包封率为 98.7%,体外释放期约为 3 周。荷有人肝癌的小鼠采用瘤内注射 PMCD 一次。治疗后第 21 天,高剂量组肿瘤生长抑制率为 72.7%,表明具有显著的抗肿瘤活性。同时,基于超声造影和微血管密度测定观察到了良好的抗血管生成作用。此外,实时荧光定量 PCR 显示血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)和血管生成素-2(Ang2)基因的表达显著下调。PMCD 的间质化疗对人肝癌异种移植的治疗效果显著且安全,降低血管生成可能是其抗肿瘤活性的最重要机制之一。

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