General Pathology Laboratory, Faculty of Medicine, University of Coimbra, Rua Larga, Coimbra, Portugal.
Biochem Biophys Res Commun. 2011 May 20;408(4):713-9. doi: 10.1016/j.bbrc.2011.04.109. Epub 2011 Apr 28.
Docetaxel and sodium selenite are well known for their anticancer properties. While resistance to docetaxel remains an obstacle in prostate cancer chemotherapy, sodium selenite, has been exploited as a new therapeutic approach. Currently, development of therapies affecting a multitude of cell targets, have been proposed as a strategy to overcome drug resistance. This association may reduce systemic toxicity counteracting a wide range of side effects. Here we report the effect of docetaxel and sodium selenite combination on the PC3 prostate cancer cell line, derived from bone metastasis. Therefore we evaluate cell growth, cell cycle progression, viability, mitochondria membrane potential, cytochrome C, Bax/Bcl2 ratio, caspase-3 expression and reactive oxygen species production. Our results suggest that sodium selenite and docetaxel combination have a synergistic effect on cell growth inhibition (67%) compared with docetaxel (22%) and sodium selenite (24%) alone. This combination also significantly induced cell death, mainly by late apoptosis vs necrosis, which is correlated with mitochondria membrane potential depletion. On the other hand, cytochrome C, Bax/Bcl2 ratio and caspase-3, known as proapoptotic factors, significantly increased in the presence of sodium selenite alone, but not in the presence of docetaxel in monotherapy or in combination with sodium selenite. These findings suggest that docetaxel and sodium selenite combination may be more effective on prostate cancer treatment than docetaxel alone warranting further evaluation of this combination in prostate cancer therapeutic approach.
多西他赛和亚硒酸钠是众所周知的抗癌药物。虽然多西他赛耐药仍然是前列腺癌化疗的一个障碍,但亚硒酸钠已被用作新的治疗方法。目前,已经提出了针对多种细胞靶点的治疗方法的开发,作为克服耐药性的一种策略。这种联合可能会降低系统毒性,从而抵消广泛的副作用。在这里,我们报告了多西他赛和亚硒酸钠联合应用于源自骨转移的 PC3 前列腺癌细胞系的效果。因此,我们评估了细胞生长、细胞周期进程、活力、线粒体膜电位、细胞色素 C、Bax/Bcl2 比值、caspase-3 表达和活性氧产生。我们的结果表明,与多西他赛(22%)和亚硒酸钠(24%)单独使用相比,多西他赛和亚硒酸钠联合使用对细胞生长抑制有协同作用(67%)。这种联合还显著诱导细胞死亡,主要通过晚期凋亡而不是坏死,这与线粒体膜电位耗竭有关。另一方面,细胞色素 C、Bax/Bcl2 比值和 caspase-3,作为促凋亡因子,在单独使用亚硒酸钠时显著增加,但在多西他赛单独治疗或与亚硒酸钠联合治疗时则没有增加。这些发现表明,多西他赛和亚硒酸钠联合应用可能比单独使用多西他赛更有效治疗前列腺癌,值得进一步评估这种联合在前列腺癌治疗方法中的应用。