Synergistic antitumor effect of TRAIL and adriamycin on the human breast cancer cell line MCF-7
Synergistic antitumor effect of TRAIL and adriamycin on the human breast cancer cell line MCF-7
复制标题
DOI：
10.1590/s0100-879x2009000900013
复制
发表时间：
2009-09-01
影响因子：
2.3
通讯作者：
Yi, C.
中科院分区：
文献类型：
--
作者：
Cui, D.D.;Huang, Y.;Yi, C.
本研究的目的是确定肿瘤坏死因子相关凋亡诱导配体（TRAIL）和阿霉素（ADM）联合对人乳腺癌细胞系MCF-7的影响，并确定潜在的细胞凋亡机制。MTT法检测细胞活力，Webb系数法评价协同效应。使用Annexin V-FITC和碘化丙啶染色流式细胞术定量细胞凋亡。RT-PCR检测TRAIL受体mRNA的表达。Western blot检测Bax和caspase-9蛋白表达的变化。MCF-7细胞对TRAIL相对耐药（IC 50> 10 μ g/mL），而MCF-7细胞对ADM敏感（IC 50 < 10 μ g/mL）。亚毒性浓度的ADM（0.5 μ g/mL）与0.1、1或10 μ g/mL的TRAIL组合对MCF-7细胞具有协同细胞毒性作用，这在TRAIL（0.1 μ g/mL）和ADM（0.5 μ g/mL）的组合中更为显著。此外，联合治疗与TRAIL和ADM显着增加细胞凋亡从9.8%（TRAIL）或17%（ADM）至38.7%，导致协同凋亡效应，这被认为是通过上调DR 4和DR 5的mRNA表达和Bax和caspase-9蛋白的表达增加介导的。这些结果表明，TRAIL和ADM的组合可能是一个有希望的治疗乳腺癌。
The aim of the present study was to determine the effect of the combination of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and adriamycin (ADM) on the human breast cancer cell line MCF-7 and to identify potential mechanisms of apoptosis. Cell viability was analyzed by the MTT assay and the synergistic effect was assessed by the Webb coefficient. Apoptosis was quantified using the annexin V-FITC and propidium iodide staining flow cytometry. The mRNA expression of TRAIL receptors was measured by RT-PCR. Changes in the quantities of Bax and caspase-9 proteins were determined by Western blot. MCF-7 cells were relatively resistant to TRAIL (IC50 > 10 mu g/mL), while MCF-7 cells were sensitive to ADM (IC50 < 10 mu g/mL). A subtoxic concentration of ADM (0.5 mu g/mL) combined with 0.1, 1, or 10 mu g/mL TRAIL had a synergistic cytotoxic effect on MCF-7 cells, which was more marked with the combination of TRAIL (0.1 mu g/mL) and ADM (0.5 mu g/mL). In addition, the combined treatment with TRAIL and ADM significantly increased cell apoptosis from 9.8% (TRAIL) or 17% (ADM) to 38.7%, resulting in a synergistic apoptotic effect, which is proposed to be mediated by up-regulation of DR4 and DR5 mRNA expression and increased expression of Bax and caspase-9 proteins. These results suggest that the combination of TRAIL and ADM might be a promising therapy for breast cancer.