Department of Food Science, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan.
Department of Leisure, Recreation and Tourism Management, Tzu Hui Institute of Technology, Pingtung 92601, Taiwan.
Int J Mol Sci. 2018 Jun 14;19(6):1769. doi: 10.3390/ijms19061769.
Cisplatin (DPP), a clinically potent antineoplastic agent, is limited by its severe adverse effects. The aim of this study was to investigate the effect of oligogalacturonides (OGA) and DDP on human lung cancer A549 cells. The combined use of OGA and DDP had a synergistic effect on the growth inhibition of A549 cells, changed the cell cycle distribution, and enhanced apoptotic response, especially in sequential combination treatment group of DDP 12 h + OGA 12 h. Western blot analyses showed that the combination treatment of OGA and DDP upregulated Bax, p53, and Caspase-3 and downregulated Bcl-2 proteins. More importantly, DDP-induced toxicity was attenuated by OGA and DDP combination treatment in normal HEK293 cells. Our data suggests that the combined use of OGA from natural sources and DDP could be an important new adjuvant therapy for lung cancer as well as offer important insights for reducing kidney toxicity of DDP and delaying the development of DDP resistance.
顺铂（DPP）是一种临床有效的抗肿瘤药物，但由于其严重的不良反应而受到限制。本研究旨在探讨寡聚半乳糖醛酸（OGA）和 DDP 对人肺癌 A549 细胞的影响。OGA 和 DDP 的联合使用对 A549 细胞的生长抑制具有协同作用，改变细胞周期分布，并增强凋亡反应，特别是在 DDP12h+OGA12h 的序贯联合治疗组中。Western blot 分析表明，OGA 和 DDP 的联合处理上调了 Bax、p53 和 Caspase-3 蛋白，下调了 Bcl-2 蛋白。更重要的是，OGA 和 DDP 的联合处理减轻了 DDP 诱导的正常 HEK293 细胞毒性。我们的数据表明，天然来源的 OGA 与 DDP 的联合使用可能是肺癌的一种重要新辅助治疗方法，并为降低 DDP 的肾毒性和延缓 DDP 耐药性的发展提供了重要的见解。
