Background/Objectives:Glycolysis and mitochondrial oxidative phosphorylation are the two major metabolic pathways for cellular ATP production. The metabolic plasticity displayed by cancer cells allows them to effectively shift between each of these pathways as a means of adapting to various growth conditions, thus ensuring their survival, proliferation and disease progression. Metabolic plasticity also provides cancer cells with the ability to circumvent many traditional monotherapies aimed at only one or the other of the major ATP-producing pathways. The purpose of this study was to determine the effectiveness of a dual treatment strategy aimed simultaneously at both pathways of ATP production in human breast cancer cells. It was hypothesized that concurrent exposure of these cells to the mitochondria-targeting chemotherapeutic agent, elesclomol, in combination with either of two glycolytic inhibitors, 2-deoxy-D-glucose or 3-bromopyruvate, would yield greater in vitro anticancer effects than those observed for any of the compounds used as a single agent.Methods:Cytotoxicity and clonogenic assays were employed to assess the survival and proliferation of MCF7 and MDA-MB-231 human breast adenocarcinoma cells exposed to the compounds alone and in combination.Results:The data obtained show that the cancer-cell-killing and antiproliferative effects of the dual treatment were significantly enhanced compared to those observed for any of the compounds alone.Conclusions:The results of this study are important in that they suggest the possibility of a novel and effective chemotherapeutic strategy for breast cancer cell killing.
背景/目的：糖酵解与线粒体氧化磷酸化是细胞产生ATP的两条主要代谢途径。癌细胞表现出的代谢可塑性使其能够根据不同的生长条件，在这两条途径之间灵活切换，从而确保其存活、增殖及疾病进展。这种代谢可塑性也使癌细胞能够规避许多仅针对单一ATP生成途径的传统单一疗法。本研究旨在探讨同时靶向两条ATP生成途径的双重治疗策略对人乳腺癌细胞的有效性。我们假设，将靶向线粒体的化疗药物艾乐司莫与两种糖酵解抑制剂（2-脱氧-D-葡萄糖或3-溴丙酮酸）中的任一种联合使用，会比单一用药产生更强的体外抗癌效果。 方法：采用细胞毒性实验和克隆形成实验，评估MCF7和MDA-MB-231人乳腺癌腺癌细胞在单独及联合用药条件下的存活与增殖情况。 结果：数据显示，双重治疗的癌细胞杀伤和抗增殖效果显著优于任何单一化合物。 结论：本研究结果具有重要意义，提示了一种可能的新型有效化疗策略用于杀伤乳腺癌细胞。
肿瘤(癌症)患者之家