ABSTRACT

Angiogenesis is the formation of new blood vessels. Angiogenesis affects cancer growth and is a useful target for cancer therapeutics. The effects of geldanamycin on angiogenesis in cases of gastric cancer are poorly understood. We investigated the effects of different doses of 17-allylamino-17-demethoxygeldanamycin (17-AGG), a semi-synthetic derivative of geldanamycin, on the interactions between cellular matrix proteins and angiogenesis factors in a gastric cancer cell line. We examined cancer cells on laminin and collagen I coated surfaces to determine their response to the angiogenic effect of these matrix molecules. We also evaluated the expression levels of VEGF, MMP-9, ES and TSP-1 using ELISA. We found that application of 17-AAG to the gastric cancer cell line on culture dish plastic decreased VEGF, TSP-1, ES and MMP-9 expression, whereas of all of these proteins were increased by laminin and collagen coating. 17-AAG currently is in clinical trial phase 2 and may be a promising drug for treatment of gastric cancer.

摘要

血管生成是新血管的形成。血管生成影响癌症生长并且是癌症治疗的有用靶标。格尔德霉素对胃癌血管生成的影响知之甚少。我们研究了不同剂量的 17-烯丙氨基-17-脱甲氧基格尔德霉素 (17-AGG)（格尔德霉素的半合成衍生物）对胃癌细胞系中细胞基质蛋白和血管生成因子之间相互作用的影响。我们检查了层粘连蛋白和 I 型胶原蛋白涂层表面上的癌细胞，以确定它们对这些基质分子的血管生成作用的反应。我们还使用 ELISA 评估了 VEGF、MMP-9、ES 和 TSP-1 的表达水平。我们发现将 17-AAG 应用于培养皿塑料上的胃癌细胞系可降低 VEGF、TSP-1、ES 和 MMP-9 的表达，而在所有这些蛋白质中，层粘连蛋白和胶原涂层都增加了。17-AAG目前处于临床试验阶段2，可能是治疗胃癌的有前途的药物。