Inhibition of Tumor Growth by Targeted Toxins in Mice is Dramatically Improved by Saponinum Album in a Synergistic Way
Inhibition of Tumor Growth by Targeted Toxins in Mice is Dramatically Improved by Saponinum Album in a Synergistic Way
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DOI：
10.1097/cji.0b013e3181ad4052
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发表时间：
2009-09-01
影响因子：
3.9
通讯作者：
Fuchs, Hendrik
中科院分区：
文献类型：
--
作者：
Bachran, Christopher;Duerkop, Horst;Fuchs, Hendrik
靶向毒素在癌症治疗中的应用仍然是一个挑战，这是由于所需的高全身剂量导致的严重副作用。在这里，我们描述了糖基化的三萜类化合物（Spn）和表皮生长因子受体（EGFR）靶向嵌合毒素（SA 2 E）的联合应用。SA 2 E对转染人EGFR的小鼠TSA肿瘤细胞的细胞毒性通过低非透化Spn浓度以协同方式增强20，000倍。皮下应用Spn和SA 2 E的BALB/c小鼠听到一个固体TSA细胞转染表皮生长因子受体肿瘤导致94%的肿瘤体积缩小与50倍低的嵌合毒素浓度相比，纯SA 2 E治疗。通过可观察到的并发症、体重、血液参数监测的副作用：组织学分析和抗体反应仅为中度，通常可逆。
The application of targeted toxins in cancer therapy remains a challenge due to the severe side effects as a consequence of the high systemic doses required. Here, we describe the combined application of a glycosylated triterpenoid (Spn) and epidermal growth factor receptor (EGFR)-targeted chimeric toxins (SA2E). The cytotoxicity of SA2E on murine TSA tumor cells transfected with human EGFR was enhanced 20,000-fold by low nonpermeabilizing Spn concentrations in a synergistic manner. Subcutaneous application of Spn and SA2E in BALB/c mice hearing a solid TSA cells transfected with epidermal growth factor receptor tumor resulted in 94% tumor volume reduction with a 50-fold lower chimeric toxin concentration compared with pure SA2E treatment. Side effects as monitored by observable complications, body weight, blood parameters: histologic analyses and antibody responses were only moderate and usually reversible.