Department of Immunology, Biochemistry and Nutrition, Warsaw Medical University, 3 Oczki Street, 02-007, Warsaw, Poland.
Department of Microbiology and Clinical Immunology, University of Warmia and Mazury, 13 Oczapowskiego Street, 10-957, Olsztyn, Poland.
Adv Exp Med Biol. 2017;1020:91-104. doi: 10.1007/5584_2017_17.
Tumor angiogenesis is an important link in the process of tumor growth and metastasis. A number of substances with an anti-angiogenic activity has been described, but their efficiency remains low. Many researchers believe that a better therapeutic effect could be achieved using a cocktail of several anti-angiogenic agents, having different points of action. A lot of synthetic and natural products of plant and animal origin have anti-tumor and anti-angiogenic properties. The aim of the present study was to evaluate the effect of some combinations of angiogenesis inhibitors on the growth and neovascularization of murine sarcoma L-1 , and on angiogenesis induced in the mouse skin by grafting of human renal cancer. The influence of theobromine, sulindac and its metabolite sulindac sulfone, chlorogenic acid, and shark liver oil on the afferent and efferent angiogenesis pathways was tested. Individually, all of these substances suppressed tumor growth and angiogenesis. Synergy was found for a combination of theobromine, sulindac, and chlorogenic acid (L-1 sarcoma tumor growth), and for theobromine with sulindac sulfone or with shark liver oil, which were given to the mice grafted with human renal cancer cells (angiogenesis). No synergistic effects were shown after preincubation with tumor cells and inhibitors.
肿瘤血管生成是肿瘤生长和转移过程中的一个重要环节。已经描述了许多具有抗血管生成活性的物质，但它们的效率仍然很低。许多研究人员认为，使用几种具有不同作用点的抗血管生成药物的鸡尾酒疗法可以获得更好的治疗效果。许多植物和动物来源的合成和天然产物具有抗肿瘤和抗血管生成特性。本研究旨在评估几种血管生成抑制剂组合对小鼠肉瘤 L-1 的生长和新生血管形成以及移植人肾癌诱导的小鼠皮肤血管生成的影响。测试了可可碱、舒林酸及其代谢物舒林酸砜、绿原酸和鲨鱼肝油对输入和输出血管生成途径的影响。这些物质单独使用时均能抑制肿瘤生长和血管生成。可可碱、舒林酸和绿原酸（L-1 肉瘤肿瘤生长）的组合以及可可碱与舒林酸砜或鲨鱼肝油的组合显示出协同作用，这些组合被给予移植了人肾癌细胞的小鼠（血管生成）。在与肿瘤细胞和抑制剂预孵育后，没有显示出协同作用。
