Targeting angiogenic processes by combination low-dose paclitaxel and radiation therapy.
Targeting angiogenic processes by combination low-dose paclitaxel and radiation therapy.
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DOI：
10.1097/00000421-200306000-00029
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发表时间：
2003-06-01
期刊：
影响因子：
--
通讯作者：
Grant, Derrick S
中科院分区：
文献类型：
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作者：
Dicker, Adam P;Williams, Torian L;Grant, Derrick S
肿瘤生长和血管生成是相互依赖的。紫杉醇和放射治疗通常用于临床，在许多疾病部位，需要高剂量的药物和放射治疗。紫杉醇（Taxol）是一种对多种人类肿瘤具有抗肿瘤活性的二萜类化合物，可能通过诱导中期阻滞（已知是细胞周期中对辐射非常敏感的阶段），增强体外电离辐射的细胞毒性效应。当紫杉醇和放射联合使用时，对紫杉醇如何影响血管生成知之甚少。我们已经评估了不同浓度的紫杉醇和辐射的组合，在体外对尼古丁诱导的血管生成，目的是确定是否可以减少辐射和紫杉醇剂量而不牺牲疗效。我们已经发现，紫杉醇抑制内皮细胞增殖，迁移，和管形成（分化）在十分之一的浓度需要达到类似的效果，对肿瘤细胞系。在与辐射相结合，抑制内皮细胞功能是累加的，增加了两倍。低剂量紫杉醇和放射治疗的组合提示了一种互补策略，具有潜在的临床分支，以靶向血管生成依赖性恶性肿瘤。
Tumor growth and angiogenesis are interdependent. Paclitaxel and radiation therapy are commonly used in the clinic, in a number of disease sites, requiring high dosages of both drug and radiation for cure. Paclitaxel (Taxol) is a diterpenoid with antitumor activity against a variety of human neoplasms and can amplify the cytotoxic effect of ionizing radiation in vitro, presumably by inducing arrest at metaphase, known to be a very radiosensitive phase of the cell cycle. Little is known about how angiogenesis is affected by paclitaxel when the combination of paclitaxel and radiation are used. We have evaluated the combination of paclitaxel and radiation at various concentrations, on cytokine-induced angiogenesis in vitro with the goal of determining whether reduction of radiation and paclitaxel doses is possible without sacrificing efficacy. We have found that paclitaxel inhibited endothelial cell proliferation, migration, and tube formation (differentiation) at one-tenth the concentration needed to achieve a similar effect on tumor cell lines. In combination with radiation, inhibition of endothelial cell function was additive and increased twofold. The combination of low-dose paclitaxel and radiation suggests a complementary strategy with potential clinical ramifications to target angiogenesis-dependent malignancies.