Ding Ning, Zhang Hong, Su Shan, Ding Yumei, Yu Xiaohui, Tang Yujie, Wang Qingfang, Liu Peishu
Department of Obstetrics and Gynecology, QiLu Hospital of Shandong University, Shangdong, China.
Department of Gynecology, The Central Hospital of Zibo, Shangdong, China.
Anticancer Agents Med Chem. 2018;18(7):1054-1063. doi: 10.2174/1871520618666171219113036.
Endometrial cancer is a common cause of death in gynecological malignancies. Cisplatin is a clinically chemotherapeutic agent. However, drug-resistance is the primary cause of treatment failure.
Emodin is commonly used clinically to increase the sensitivity of chemotherapeutic agents, yet whether Emodin promotes the role of Cisplatin in the treatment of endometrial cancer has not been studied.
CCK-8 kit was utilized to determine the growth of two endometrial cancer cell lines, Ishikawa and HEC-IB. The apoptosis level of Ishikawa and HEC-IB cells was detected by Annexin V / propidium iodide double-staining assay. ROS level was detected by DCFH-DA and NADPH oxidase expression. Expressions of drug-resistant genes were examined by real-time PCR and Western blotting.
Emodin combined with Cisplatin reduced cell growth and increased the apoptosis of endometrial cancer cells. Co-treatment of Emodin and Cisplatin increased chemosensitivity by inhibiting the expression of drugresistant genes through reducing the ROS levels in endometrial cancer cells. In an endometrial cancer xenograft murine model, the tumor size was reduced and animal survival time was increased by co-treatment of Emodin and Cisplatin.
This study demonstrates that Emodin enhances the chemosensitivity of Cisplatin on endometrial cancer by inhibiting ROS-mediated expression of drug-resistance genes.
子宫内膜癌是妇科恶性肿瘤中常见的死亡原因。顺铂是一种临床化疗药物。然而，耐药性是治疗失败的主要原因。
临床常用大黄素提高化疗药物的敏感性，但大黄素是否促进顺铂在子宫内膜癌治疗中的作用尚未见研究。
采用CCK-8试剂盒检测两种子宫内膜癌细胞系Ishikawa和HEC-IB的生长情况。采用Annexin V/碘化丙啶双染法检测Ishikawa和HEC-IB细胞的凋亡水平。用DCFH-DA检测ROS水平，检测NADPH氧化酶表达。通过实时PCR和蛋白质印迹法检测耐药基因的表达。
大黄素联合顺铂可降低子宫内膜癌细胞的生长并增加其凋亡。大黄素与顺铂联合治疗通过降低子宫内膜癌细胞中的ROS水平，抑制耐药基因的表达，从而增加化疗敏感性。在子宫内膜癌异种移植小鼠模型中，大黄素与顺铂联合治疗可减小肿瘤大小并延长动物存活时间。
本研究表明，大黄素通过抑制ROS介导的耐药基因表达增强顺铂对子宫内膜癌的化疗敏感性。
