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在肺泡横纹肌肉瘤中具有协同抗肿瘤特性。

Synergistic Antitumour Properties of in Alveolar Rhabdomyosarcoma.

机构信息

Department of Paediatric Oncology/Haematology, Otto-Heubner Centre for Paediatric and Adolescent Medicine (OHC), Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.

EPO GmbH, Experimental Pharmacology & Oncology, Robert-Rössle-Str. 10, 13125 Berlin-Buch, Germany.

出版信息

J Immunol Res. 2017;2017:4874280. doi: 10.1155/2017/4874280. Epub 2017 Jul 16.

Abstract

Aqueous mistletoe extracts from the European mistletoe () contain mainly mistletoe lectins and viscotoxins as cytotoxic compounds. Lipophilic triterpene acids, which do not occur in conventional mistletoe preparations, were solubilised with -cyclodextrins. The combination of an aqueous extract () and a triterpene-containing extract () recreated a whole mistletoe extract (). These extracts were tested on rhabdomyosarcoma in vitro, ex vivo, and in vivo with regard to anticancer effects. and inhibited cell proliferation and induced apoptosis effectively in a dose-dependent manner in vitro and ex vivo, whereas showed only moderate inhibitory effects. proved to be more effective than the single extracts and displayed a synergistic effect in vitro and a stronger effect in vivo. induced apoptosis via the extrinsic and intrinsic pathways, evidenced by the loss of mitochondrial membrane potential and activation of CASP8 and CASP9. CASP10 inhibitor inhibited apoptosis effectively, emphasising the importance of CASP10 in -induced apoptosis. Additionally, changed the ratio of apoptosis-associated proteins by downregulation of antiapoptotic proteins such as XIAP and BIRC5, thus shifting the balance towards apoptosis. effectively reduced tumour volume in patient-derived xenografts in vivo and may be considered a promising substance for rhabdomyosarcoma therapy.

摘要

水培槲寄生提取物()主要含有作为细胞毒性化合物的槲寄生凝集素和粘性毒素。脂溶性三萜酸与常规槲寄生制剂中不含有,而是用 -环糊精溶解。水提取物()和含有三萜的提取物()的组合重新生成了全槲寄生提取物()。这些提取物在体外、离体和体内针对横纹肌肉瘤进行了抗癌效果测试。和在体外和离体以剂量依赖性方式有效抑制细胞增殖并诱导细胞凋亡,而仅显示出中等抑制作用。证明比单一提取物更有效,在体外显示协同作用,在体内显示更强的作用。通过外在和内在途径诱导细胞凋亡,这可通过线粒体膜电位丧失和 CASP8 和 CASP9 的激活来证明。CASP10 抑制剂有效地抑制了细胞凋亡,强调了 CASP10 在 -诱导细胞凋亡中的重要性。此外,通过下调抗凋亡蛋白(如 XIAP 和 BIRC5)改变了与凋亡相关的蛋白的比例,从而使平衡向凋亡倾斜。在体内患者来源的异种移植中有效减少了肿瘤体积,并且可以被认为是横纹肌肉瘤治疗的有前途的物质。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3139/5534308/f7e528ead26f/JIR2017-4874280.001.jpg

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