Pancreatic Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Pancreatic Cancer, including details on symptoms, causes, treatment, information. | ||||||||
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Synthetic serine protease inhibitor, gabexate mesilate, prevents nuclear factor-kappaB activation and increases TNF-alpha-mediated apoptosis in human pancreatic cancer cells.Takahashi H, Funahashi H, Sawai H, Matsuo Y, Yamamoto M, Okada Y, Takeyama H, Manabe T Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, 467-8601, Nagoya, Japan. takahasi@med.nagoya-cu.ac.jp Gabexate mesilate (GM), a synthetic serine protease inhibitor, suppresses nuclear factor-kappaB (NF-kappaB) activity in human monocytes or human umbilical vein endothelial cells (HUVECs). In this study we examine whether GM also suppresses NF-kappaB activation and induces apoptosis in human pancreatic cancer cell lines. The addition of tumor necrosis factor alpha (TNF-alpha) did not change the rates of growth of BxPC-3 and MIA PaCa-2. However, in the presence of GM and TNF-alpha, proliferation decreased in a dose-dependent manner. GM- and TNF-alpha-treated cells exhibited morphologic changes indicative of apoptosis, including chromatin condensation and nuclear fragmentation. The NF-kappaB activity of both cell lines was increased by the addition of TNF-alpha, while TNF-alpha-induced NF-kappaB activity was suppressed by prestimulation with GM in a dose-dependent manner. Caspase 3 and 7 activity was significantly increased by TNF-alpha with GM stimulation. Furthermore, GM also suppressed the invasive potential of both cell lines. These results indicate that GM inhibits TNF-alpha-induced NF-kappaB activation and enhances apoptosis in human pancreatic cancer cell lines. Published 6 September 2007 in Dig Dis Sci, 52(10): 2646-52.
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