Paclitaxel (Taxol): An inhibitor of angiogenesis in a highly vascularized transgenic breast cancer
Paclitaxel (Taxol): An inhibitor of angiogenesis in a highly vascularized transgenic breast cancer
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DOI：
10.1089/cbr.1999.14.31
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发表时间：
1999-02-01
影响因子：
3.4
通讯作者：
Cheung, AT
中科院分区：
文献类型：
--
作者：
Lau, DH;Xue, L;Cheung, AT
紫杉醇是微管聚合的促进剂和放射增敏剂，是目前实体瘤治疗中活性较高的抗癌药物之一。在这项研究中，我们发现紫杉醇具有抗血管生成的特性，与高度血管化的转基因小鼠乳腺癌(Met-1)中血管内皮生长因子(VEGF)的下调有关。紫杉醇非细胞毒性剂量分别为0、3和6 mg/kg/d，对荷瘤裸鼠进行连续5天的腹腔注射。紫杉醇以剂量依赖的方式显著降低肿瘤内血管生成的程度(以微血管弯曲和微血管密度表示)，紫杉醇还抑制移植于裸鼠或维持在细胞培养中的Met-1细胞中血管内皮生长因子的表达。这些结果表明，与下调血管内皮生长因子相关的抗血管生成是紫杉醇的另一种作用模式。
Paclitaxel (Taxol), a promoter of microtubule polymerization and a radiosensitizing agent, is one of the more active anticancer drugs in the current treatment of solid tumors. In this study, we show that paclitaxel possesses an antiangiogenic property, associated with a down-regulation of vascular endothelial growth factor (VEGF) in a highly-vascularized transgenic murine breast cancer (Met-1). Paclitaxel, at non-cytotoxic doses of 0, 3 and 6 mg/kg/day, was administered intraperitoneally for 5 days to nude mice bearing the Met-1 breast tumor. Extent of intratumoral angiogenesis, as indicated by microvessel tortuosity and microvessel density, was significantly reduced by paclitaxel in a dose-dependent manner Paclitaxel also suppressed expression of VEGF in the Met-1 cells transplanted in nude mice or maintained in cell culture. These results indicate that antiangiogenesis associated with a down-regulation of VEGF is an additional mode of action of paclitaxel.