Anti-tumoural effects of PlgK1-5 are directly linked to reduced ICAM expression, resulting in hepatoma cell apoptosis
Anti-tumoural effects of PlgK1-5 are directly linked to reduced ICAM expression, resulting in hepatoma cell apoptosis
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DOI：
10.1007/s00384-012-1418-6
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发表时间：
2012-03
影响因子：
2.8
通讯作者：
V. Schmitz;T. Sauerbruch;E. Raskopf
中科院分区：
文献类型：
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作者：
V. Schmitz;T. Sauerbruch;E. Raskopf
目的血管抑素和血管抑素样分子被称为抗血管生成因子，其抑制内皮细胞功能，导致肿瘤生长减少。最近的数据表明，这些分子，特别是PlgK 1 -5，直接影响肿瘤细胞，这可以解释PlgK 1 -5的强大抗肿瘤作用。因此，我们分析了PlgK 1 -5是否改变肿瘤细胞的功能和细胞粘附分子在小鼠和人肝癌细胞在体外和体内的表达水平。MethodsFirst，在体内的皮下肿瘤模型中的肿瘤生长，增殖和凋亡的影响进行了研究。在体外，PlgK 1 -5对肿瘤细胞凋亡，克隆扩张，迁移，相应的ICAM的表达和细胞内信号转导在小鼠Hepa 129和人HuH 7肝癌cells的影响进行了analysed.ResultsIn体内，皮下肿瘤的生长减少了75%，PlgK 1 -5治疗的动物相比，控制。这伴随着肿瘤细胞凋亡增加（高达33%）和肿瘤细胞增殖减少（高达21%）。在体外，PlgK 1 -5诱导肝癌细胞凋亡，对应于增加caspase-8切割和减少AKT磷酸化。迁移和克隆扩张也减少了PlgK 1 -5处理的Hepa 129，相应的ICAM表达水平降低conclusionsHere，我们表明，PlgK 1 -5直接影响肿瘤细胞通过减少细胞粘附导致至少部分凋亡。这是通过改变细胞内信号转导和激活半胱天冬酶级联介导的。这些发现进一步强调了PlgK 1 -5在治疗HCC中的潜在治疗作用。
PurposeAngiostatin 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.MethodsFirst, 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.ResultsIn 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.ConclusionsHere, 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.