Synthetic serine protease inhibitor, Gabexate mesilate, prevents nuclear Factor-κB activation and increases TNF-α-Mediated apoptosis in human pancreatic cancer cells
Synthetic serine protease inhibitor, Gabexate mesilate, prevents nuclear Factor-κB activation and increases TNF-α-Mediated apoptosis in human pancreatic cancer cells
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DOI：
10.1007/s10620-006-9654-7
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发表时间：
2007-10-01
影响因子：
3.1
通讯作者：
Manabe, Tadao
中科院分区：
文献类型：
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作者：
Takahashi, Hiroki;Funahashi, Hitoshi;Manabe, Tadao
甲磺酸加贝酯（GM）是一种合成丝氨酸蛋白酶抑制剂，可抑制人单核细胞或人脐静脉内皮细胞（HUVEC）中的核因子-κ B（NF-κ B）活性。在这项研究中，我们检查是否GM也抑制NF-κ B B激活和诱导人胰腺癌细胞系的凋亡。添加肿瘤坏死因子α（TNF-α）并没有改变BxPC-3和MIA PaCa-2的生长速率。然而，在GM和TNF-α的存在下，增殖以剂量依赖性方式降低。GM和TNF-α处理的细胞表现出凋亡的形态学变化，包括染色质浓缩和核碎裂。两种细胞系的NF-κ B活性均被加入TNF-α所增加，而TNF-α诱导的NF-κ B活性被GM以剂量依赖性方式预刺激所抑制。Caspase 3和7的活性显着增加TNF-α与GM刺激。此外，GM还抑制了两种细胞系的侵袭潜力。这些结果表明，GM抑制TNF-α诱导的NF-κ B活化并增强人胰腺癌细胞系的凋亡。
Gabexate mesilate ( GM), a synthetic serine protease inhibitor, suppresses nuclear factor-kappa B (NF-kappa B) activity in human monocytes or human umbilical vein endothelial cells (HUVECs). In this study we examine whether GM also suppresses NF-kappa B 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-kappa Bactivity of both cell lines was increased by the addition of TNF-alpha, while TNF-alpha-induced NF-kappa B 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-kappa B activation and enhances apoptosis in human pancreatic cancer cell lines.