Molecular Pathology Unit, Institute for Medical Research, Jalan Pahang, Kuala Lumpur, 50588, Malaysia.
Cancer Cell Int. 2012 Jul 18;12(1):34. doi: 10.1186/1475-2867-12-34.
Nasopharyngeal carcinoma (NPC) is a unique tumour of epithelial origin with a distinct geographical distribution, genetic predisposition and environmental as well as dietary influence as aetiological factors. Standard NPC treatment regimes, such as radiotherapy and concurrent chemotherapy with cytotoxic drugs, can produce undesirable complications often associated with significant toxicity. Here, we report the effects of a widely distributed flavonoid, quercetin, on cell proliferation, apoptosis and cell cycle arrest. The effects of combining quercetin and cisplatin on human NPC cells were explored.
Cell proliferation was monitored by the dynamic, impedance-based cell analyzer (xCELLigence system) and the MTS assay. Ki67 proliferation antigen and fatty acid synthase (FASN) level was examined by Western blotting. Flow cytometry was also carried out to study the effects of quercetin on cell cycle and apoptosis status.
At 100 μM, quercetin inhibited cell proliferation and decreased expression of FASN and Ki67 antigen. Cell cycle analysis revealed a substantial increase in the proportion of cells in the G2/M phase. We also demonstrated the enhanced cytotoxic effects of quercetin treatment in concomitant with the chemotherapeutic drug, cisplatin, in cultured NPC cells. The combination index (CI) value of quercetin-cisplatin combination was < 1, indicating synergism.
Our study showed that quercetin exhibited synergistic effects with cisplatin against NPC cells. Dose-reduction index (DRI) values > 1 implied the possibility of reducing the cisplatin dosage required to treat NPC, with the addition of quercetin. In turn, this could reduce the risk of cisplatin-associated toxicity. The potential of combining quercetin with cisplatin as a chemotherapeutic strategy for treatment of NPC should be explored further.
鼻咽癌（NPC）是一种独特的上皮来源肿瘤，具有独特的地理分布、遗传易感性以及环境和饮食影响等病因学因素。标准的 NPC 治疗方案，如放射治疗和联合细胞毒性药物的化疗，可能会产生不良并发症，通常与显著的毒性有关。在这里，我们报告了一种广泛分布的黄酮类化合物槲皮素对细胞增殖、凋亡和细胞周期停滞的影响。研究了槲皮素与顺铂联合对人 NPC 细胞的影响。
通过动态、基于阻抗的细胞分析仪（xCELLigence 系统）和 MTS 测定法监测细胞增殖。通过 Western 印迹法检测 Ki67 增殖抗原和脂肪酸合酶（FASN）水平。还进行了流式细胞术以研究槲皮素对细胞周期和凋亡状态的影响。
在 100μM 时，槲皮素抑制细胞增殖并降低 FASN 和 Ki67 抗原的表达。细胞周期分析显示 G2/M 期细胞比例显著增加。我们还证明了在培养的 NPC 细胞中，与化疗药物顺铂联合使用时，槲皮素治疗可增强细胞毒性作用。槲皮素-顺铂联合的组合指数（CI）值<1，表明存在协同作用。
我们的研究表明，槲皮素与顺铂对 NPC 细胞表现出协同作用。剂量减少指数（DRI）值>1 表明，在添加槲皮素的情况下，有可能减少治疗 NPC 所需的顺铂剂量。反过来，这可以降低顺铂相关毒性的风险。应该进一步探索将槲皮素与顺铂联合作为治疗 NPC 的化疗策略的潜力。
