Effects of activation of AMPK on human breast cancer cell lines with different genetic backgrounds
Effects of activation of AMPK on human breast cancer cell lines with different genetic backgrounds
复制标题
DOI：
10.3892/ol.2011.458
复制
发表时间：
2012-01-01
期刊：
影响因子：
2.9
通讯作者：
Dobson, Pauline R. M.
中科院分区：
文献类型：
--
作者：
El-Masry, Omar S.;Brown, Barry L.;Dobson, Pauline R. M.
乳腺癌仍然是一个治疗挑战，这加强了对新药物靶点的研究。AMP激活蛋白激酶（AMPK）信号通路正在成为具有干预潜力的途径。我们通过研究AMPK对p53和雌激素受体（ER）状态不同的三种乳腺癌细胞系（MCF-7、MDA-MB-231和T47 D）的增殖、凋亡和线粒体膜电位的影响，评估AMPK作用对乳腺癌细胞的可能不同影响。5-氨基咪唑甲酰胺核糖核苷酸（AICAR）和苯丙氨酸激活AMPK在所有乳腺癌细胞系中引起明确的抗增殖作用，但敏感性不同。然而，抗增殖作用伴随着不同细胞之间的不同反应，在T47 D细胞中具有显著的细胞周期阻滞作用，在MCF-7和MDA-MB-231细胞中具有凋亡作用。线粒体凋亡途径可能参与所有细胞系。这些结果表明，AMPK可能作为乳腺癌的治疗靶点，但可能依赖于癌细胞的遗传背景。
Breast cancer remains a therapeutic challenge, and this has intensified the search for new drug targets. The AMP-activated protein kinase (AMPK) signalling pathway is emerging as having potential for intervention. We assessed the possible different effects of AMPK action on breast cancer cells by studying their impact on proliferation, apoptosis and the mitochondrial membrane potential in three breast cancer cell lines (MCF-7, MDA-MB-231 and T47D) differing in their p53 and estrogen receptor (ER) status. Activation of AMPK by 5-aminoimidazole carboxamide ribonucleotide (AICAR) and phenformin elicited clear anti-proliferative effects in all breast cancer cell lines, but with differences in sensitivity. However, the anti-proliferative effects were accompanied by varying responses between the different cells, with a marked cell cycle arrest effect in T47D cells and an apoptotic effect in MCF-7 and MDA-MB-231 cells. The mitochondrial apoptotic pathway was potentially involved in all cell lines. These results suggest that AMPK potentially serves as a therapeutic target in breast cancer, but one which may be dependent on the genetic background of the cancer cells.