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

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.

KEYWORDS:

• 17-allylamino-17-demethoxygeldanamycin
• angiogenesis
• cell matrix
• endostatin
• gastric cancer
• geldanamycin
• metalloproteinases
• thrombospondin
• vascular endothelial growth factor

Disclosure statement

The authors report no conflict of interest.