Zheng Ai-Wen, Chen Ya-Qing, Zhao Ling-Qin, Feng Jian-Guo
Department of Gynecologic Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China.
Cancer Research Institute, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China.
Oncol Lett. 2017 Jun;13(6):4974-4978. doi: 10.3892/ol.2017.6031. Epub 2017 Apr 13.
Ovarian cancer is the most lethal type of gynecological cancer and is the fifth leading cause of cancer-associated mortality in females globally. The majority of patients with ovarian cancer suffer from recurrent, progressive disease, due to the acquisition of a resistance phenotype towards various conventional chemotherapy drugs. Although paclitaxel has been demonstrated to be effective against ovarian tumors, there have been reports of the development of a resistant phenotype against Taxol treatment. The multidrug resistance (MDR)-1/P-glycoprotein has previously been demonstrated to be associated with the acquisition of paclitaxel resistance in certain ovarian tumors. Therefore, the screening of novel drug candidates able to target MDR-1 in ovarian cancer cells and increase the sensitivity to Taxol is required in order to improve the treatment of this disease. In the present study, the underlying mechanisms by which the dietary flavonoid myricetin enhances the cytotoxic potential of paclitaxel in ovarian cancer cells, was investigated. It was observed that myricetin induced significant cytotoxicity in A2780 and OVCAR3 ovarian cancer cells, with the IC50 value obtained at 25 µM. Myricetin treatment also resulted in the induction of apoptosis in the two cell lines, accompanied by the modulation of certain pro- and anti-apoptotic markers. It was also determined that the pre-incubation of ovarian cancer cells with a lower dose of myricetin was able to increase the cytotoxicity of paclitaxel, due to the significant downregulation of MDR-1 in these cells.
卵巢癌是最致命的妇科癌症类型，也是全球女性癌症相关死亡率的第五大主要原因。大多数卵巢癌患者患有复发性、进行性疾病，这是由于对各种传统化疗药物产生了耐药表型。尽管紫杉醇已被证明对卵巢肿瘤有效，但已有报道称出现了对紫杉醇治疗的耐药表型。多药耐药（MDR）-1/P-糖蛋白先前已被证明与某些卵巢肿瘤中紫杉醇耐药性的获得有关。因此，需要筛选能够靶向卵巢癌细胞中MDR-1并增加对紫杉醇敏感性的新型候选药物，以改善这种疾病的治疗。在本研究中，研究了膳食类黄酮杨梅素增强紫杉醇对卵巢癌细胞细胞毒性潜力的潜在机制。观察到杨梅素在A2780和OVCAR3卵巢癌细胞中诱导了显著的细胞毒性，IC50值为25μM。杨梅素处理还导致这两种细胞系发生凋亡，同时伴有某些促凋亡和抗凋亡标志物的调节。还确定，用较低剂量的杨梅素预孵育卵巢癌细胞能够增加紫杉醇的细胞毒性，这是由于这些细胞中MDR-1的显著下调。
