Discipline of Biomedical Science, School of Medical Sciences, Sydney Medical School, The University of Sydney, Cumberland Campus C42, 75 East Street, Lidcombe, NSW 1825, Australia.
Anticancer Res. 2011 Nov;31(11):3789-97.
The development of drug resistance remains one of the major hurdles in cancer chemotherapy, particularly so for ovarian cancer. Combination of drugs acting synergistically in combination can offer a means of overcoming drug resistance. In this study, two tumour-active phytochemicals, quercetin and thymoquinone, were combined with two platinum drugs, cisplatin and oxaliplatin, with the aim of providing a means of overcoming drug resistance. Two human epithelial ovarian cancer cell lines, A2780 and its cisplatin-resistant form (A2780(cisR)) were treated with binary combinations of cisplatin and oxaliplatin with quercetin and thymoquinone using three sequences of administration. Cell viability was quantified using the (MTT) reduction assay. The combined drug action was analysed based on the equations derived by Chou and Talalay (1984). Greatest synergism was observed when the phytochemical was added first followed by platinum drug 2 h later and the least synergism (often additive to antagonistic) was observed when the two compounds were administered as a bolus. It is suggested that the addition of the phytochemical 2 h before platinum drug may sensitize cancer cells to platinum action, thus offering a means of overcoming drug resistance. The results may be highly significant clinically if found to be confirmed in vivo.
耐药性的发展仍然是癌症化疗中的主要障碍之一，尤其是卵巢癌。协同作用的药物联合使用可以提供克服耐药性的方法。在这项研究中，两种具有肿瘤活性的植物化学物质槲皮素和百里醌与两种铂类药物顺铂和奥沙利铂联合使用，旨在提供克服耐药性的方法。使用三种给药顺序，用顺铂和奥沙利铂与槲皮素和百里醌的二元组合处理两种人上皮性卵巢癌细胞系 A2780 和其顺铂耐药形式（A2780(cisR)）。使用（MTT）还原测定法定量细胞活力。根据 Chou 和 Talalay（1984 年）推导出的方程分析联合药物作用。当首先添加植物化学物质，然后 2 小时后添加铂类药物时，观察到最大协同作用，而当两种化合物作为单次剂量给药时，观察到协同作用最小（通常是相加到拮抗）。这表明在铂类药物之前 2 小时添加植物化学物质可能使癌细胞对铂类药物敏感，从而提供克服耐药性的方法。如果在体内得到证实，这些结果在临床上可能具有重要意义。
