Department of Epidemiology, Mailman School of Public Health, Columbia University.
Department of Medicine, College of Physicians and Surgeons, Columbia University.
Integr Cancer Ther. 2012 Sep;11(3):243-50. doi: 10.1177/1534735412439749. Epub 2012 Apr 26.
BACKGROUND/HYPOTHESES: Doxorubicin is a standard adjuvant therapy for early-stage breast cancer, and it significantly improves disease-free and overall survival. However, 3% to 20% of breast cancer patients develop chronic cardiomyopathic changes and congestive heart failure because of doxorubicin therapy. Doxorubicin-induced cardiotoxicity is thought to be due to the increased generation of reactive oxygen species within cardiac myocyte mitochondria. Coenzyme Q10 (CoQ10) is a lipid-soluble antioxidant that may protect against mitochondrial reactive oxygen species and thus prevent doxorubicin-induced cardiotoxicity. Despite the potential benefits of CoQ10 in preventing cardiotoxicity, it is not known if CoQ10 diminishes the antineoplastic effects of doxorubicin therapy.
In vitro cell culture experiments.
Breast cancer cell lines (MDA-MB-468 and BT549) were tested for their ability to uptake exogenous CoQ10 using high-performance liquid chromatography. Breast cancer cell lines were then treated with doxorubicin and a range of CoQ10 concentrations to determine the effect of CoQ10 on doxorubicin's cytotoxicity.
This study demonstrated that intracellular and mitochondrial CoQ10 concentrations increased substantially as higher exogenous concentrations were administered to breast cancer cells. CoQ10 had no effect on the ability of doxorubicin to induce apoptosis or inhibit growth or colony formation in both the cell lines tested when applied over a wide dose range, which encompassed typical basal plasma levels and plasma levels above those typically achieved by supplemented patients.
The clinical testing of CoQ10 as a supplement to prevent doxorubicin-induced cardiotoxicity requires confidence that it does not decrease the efficacy of chemotherapy. These results support the hypothesis that CoQ10 does not alter the antineoplastic properties of doxorubicin. Further in vivo studies, as well as combination chemotherapy studies, would be reassuring before a large-scale clinical testing of CoQ10 as a cardioprotective drug.
背景/假设：多柔比星是早期乳腺癌的标准辅助治疗药物，可显著提高无病生存率和总生存率。然而，3%至 20%的乳腺癌患者因多柔比星治疗而发生慢性心肌病改变和充血性心力衰竭。多柔比星诱导的心脏毒性被认为是由于心肌细胞线粒体中活性氧的生成增加所致。辅酶 Q10（CoQ10）是一种脂溶性抗氧化剂，可能有助于防止线粒体活性氧的产生，从而预防多柔比星诱导的心脏毒性。尽管 CoQ10 在预防心脏毒性方面具有潜在益处，但尚不清楚 CoQ10 是否会降低多柔比星治疗的抗肿瘤作用。
体外细胞培养实验。
使用高效液相色谱法测试乳腺癌细胞系（MDA-MB-468 和 BT549）摄取外源性 CoQ10 的能力。然后用多柔比星和一系列 CoQ10 浓度处理乳腺癌细胞系，以确定 CoQ10 对多柔比星细胞毒性的影响。
本研究表明，随着外源性 CoQ10 浓度的增加，乳腺癌细胞内和线粒体 CoQ10 浓度显著增加。当在广泛的剂量范围内应用 CoQ10 时，CoQ10 对多柔比星诱导的细胞凋亡或抑制生长或集落形成的能力没有影响，所测试的细胞系中应用的剂量范围包括典型的基础血浆水平和高于通常通过补充患者达到的血浆水平。
作为预防多柔比星诱导心脏毒性的补充剂，临床测试 CoQ10 需要有信心它不会降低化疗的疗效。这些结果支持 CoQ10 不会改变多柔比星抗肿瘤特性的假设。在大规模临床测试 CoQ10 作为心脏保护药物之前，还需要进行进一步的体内研究以及联合化疗研究。
