葡萄孢霉素
细胞凋亡
LY294002型
程序性细胞死亡
细胞生物学
黑色素瘤
生物
活力测定
半胱氨酸蛋白酶
UVB诱导细胞凋亡
癌症研究
细胞松弛素B
细胞培养
细胞
PI3K/AKT/mTOR通路
信号转导
生物化学
蛋白激酶C
遗传学
作者
Jędrzej Małecki,Anna Bentke,Barbara Ostrowska,Piotr Laidler
出处
期刊:Melanoma Research
[Ovid Technologies (Wolters Kluwer)]
日期:2010-02-01
卷期号:20 (1): 52-58
被引量:14
标识
DOI:10.1097/cmr.0b013e328332f1e6
摘要
Many of the current anticancer therapies rely on the induction of apoptosis, and several mechanisms that protect cells against apoptosis may be upregulated in tumors. A growing body of evidence suggests that single drugs with a clearly defined intracellular target may be less efficient in arresting tumor growth and induction of apoptosis than multitargeted strategies. To prove that this is also the case for melanoma, we studied five cell lines, which represent different stages of tumor progression. We tested cell viability, terminal dUTP nick-end labeling and activation of caspase-3 upon exposure to cytochalasin D, LY294002 and olomoucine, added either alone or in various combinations. The obtained data were compared with effects caused by staurosporine. The results show that whereas staurosporine efficiently induced apoptosis in all tested melanoma cell lines, the other drugs had only moderate effects when administered alone. In contrast, the combinations of drugs were more effective in inducing caspase-3 activity and reducing cell viability. In particular, the triple combination of cytochalasin D+LY294002+olomoucine was almost as effective as staurosporine in inducing caspase-3 activity and apoptosis. These results prove that it is possible to design new pharmacological strategies that will effectively induce caspase-3 activity and apoptosis in melanoma. The possible explanations of the observed synergy between the tested drugs are also discussed.
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