Anti-tumoural effects of PlgK1-5 are directly linked to reduced ICAM expression, resulting in hepatoma cell apoptosis

作者：Schmitz Volker; Sauerbruch Tilman; Raskopf Esther^*

来源：International Journal of Colorectal Disease, Clinical and Molecular Gastroenterology and Surgery, 2012, 27(8): 1029-1038.

DOI：10.1007/s00384-012-1418-6

• PlgK1-5
• Apoptosis
• HCC
• tumour growth
• ICAM expression

Angiostatin and angiostatin-like molecules are known as anti-angiogenic factors, which inhibit endothelial cell functions resulting in reduced tumour growth. Recent data indicate that these molecules, especially PlgK1-5, directly affect tumour cells, which could explain the strong anti-tumoural effects of PlgK1-5. Therefore, we have analysed whether PlgK1-5 alters tumour cell functions and expression levels of cell adhesion molecules in murine and human hepatoma cells in vitro and in vivo. %26lt;br%26gt;First, effects on tumour growth, proliferation and apoptosis were investigated in vivo in a subcutaneous tumour model. In vitro, effects of PlgK1-5 on tumour cell apoptosis, clonal expansion, migration, corresponding ICAM expression and intracellular signal transduction in murine Hepa129 and human HuH7 hepatoma cells have been analysed. %26lt;br%26gt;In vivo, subcutaneous tumour growth was reduced by 75% in PlgK1-5-treated animals compared to the controls. This was accompanied by increased tumour cell apoptosis (up to 33%) and decreased tumour cell proliferation (by up to 21%). In vitro, PlgK1-5 induced apoptosis in hepatoma cells, corresponding to increased caspase-8 cleavage and reduced AKT phosphorylation. Migration and clonal expansion was also diminished in PlgK1-5-treated Hepa129, corresponding to decreased ICAM expression levels. %26lt;br%26gt;Here, we show that PlgK1-5 directly affects tumour cells by decreasing cell adhesion resulting-at least partly-in apoptosis. This is mediated by altered intracellular signal transduction and by activation of the caspase cascade. These findings further underscore the potential therapeutic role of PlgK1-5 in the treatment of HCC.

• 出版日期2012-8