Effect of geldanamycin on the expression of the matrix molecules and angiogenetic factors in a gastric cancer cell line.

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.

Effects of caffeic acid phenethyl ester on matrix molecules and angiogenetic and anti-angiogenetic factors in gastric cancer cells cultured on different substrates.

Migration, invasion, metastasis and angiogenesis associated with cancer depend on the surrounding microenvironment. Angiogenesis, the growth of new capillaries, is a regulator of cancer growth and a useful target for cancer therapy. We examined matrix protein interactions in a gastric cancer cell culture that was treated with different doses of caffeic acid (3,4-dihydroxycinnamic acid) phenethyl ester (CAPE). We also investigated the relations among the levels of vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), endostatin (ES) and trombospondin-1 (TSP-1). Cytotoxity of CAPE was measured using the 3-(4,5-dmethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. We examined the behavior of cells on laminin and collagen I coated surfaces in response to the angiogenic effect of these matrix molecules. We examined the protein alterations of these matrix molecules immunohistochemically and measured the levels of VEGF, MMP-9, ES and TSP-1 using the ELISA test. We showed that application of CAPE to the gastric cancer cell line on tissue culture plastic, laminin and collagen I significantly decreased the VEGF and MMP-9 protein levels. We found that TSP-1 levels were increased significantly in the gastric cancer cells after application of CAPE. The protein levels of gastric cancer cells also were increased significantly when tissue was cultured on laminin and collagen I. Application of CAPE to cells on laminin or collagen I coated surfaces significantly increased all of the proteins except ES. ES levels were increased on the collagen I covered surfaces, but the laminin surface decreased the levels of ES significantly. We demonstrated the beneficial effect of CAPE on a gastric cancer cell line including inhibition of proliferation and induction of some proteins that might be related to decreased angiogenesis.