MiR-593 mediates curcumin-induced radiosensitization of nasopharyngeal carcinoma cells via MDR1
MiR-593 mediates curcumin-induced radiosensitization of nasopharyngeal carcinoma cells via MDR1
复制标题
MiR-593通过MDR1介导姜黄素诱导的鼻咽癌细胞放射增敏
DOI：
10.3892/ol.2016.4438
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发表时间：
2016-06-01
期刊：
影响因子：
2.9
通讯作者：
Fan, Qin
中科院分区：
文献类型：
--
作者：
Fan, Haoning;Shao, Meng;Fan, Qin
姜黄素（Curcumin，Cur）对多种恶性肿瘤具有放射增敏作用。本研究探讨Cur对鼻咽癌细胞的放射增敏作用及其机制是否与microRNA-593（miR-593）和多药耐药基因1（MDR 1）有关。进行克隆形成试验以测量放射增敏作用。通过定量聚合酶链反应（qPCR）或western blot分析miR-593和MDR 1的表达。建立移植性肿瘤模型，以确定体内放射增敏作用。构建了一种基于双磷酸酶的报告基因，以评估miR-593与MDR 1的3' UTR上推定靶位点的直接结合的影响。克隆形成实验表明Cur可增强细胞的放射敏感性。Cur（100 mg/kg）联合4戈伊照射抑制了体内移植性肿瘤模型的生长，与单独放疗组相比，抑制率更高。这些结果表明，Cur对鼻咽癌细胞具有放射增敏作用; Cur上调miR-593表达可导致MDR 1表达降低，这可能促进鼻咽癌细胞的放射增敏作用。
Curcumin (Cur) exhibits radiosensitization effects to a variety of malignant tumors. The present study investigates the radiosensitizing effect of Cur on nasopharyngeal carcinoma (NPC) cells and whether its mechanism is associated with microRNA-593 (miR-593) and multidrug resistance gene 1 (MDR1). A clonogenic assay was performed to measure the radiosensitizing effect. The expression of miR-593 and MDR1 was analyzed by quantitative polymerase chain reaction (qPCR) or western blot assay. A transplanted tumor model was established to identify the radiosensitizing effect in vivo. A luciferase-based reporter was constructed to evaluate the effect of direct binding of miR-593 to the putative target site on the 3' UTR of MDR1. The clonogenic assay showed that Cur enhanced the radiosensitivity of cells. Cur (100 mg/kg) combined with 4 Gy irradiation inhibited the growth of a transplanted tumor model in vivo, resulting in the higher inhibition ratio compared with the radiotherapy-alone group. These results demonstrated that Cur had a radiosensitizing effect on NPC cells in vivo and in vitro; Cur-mediated upregulation of miR-593 resulted in reduced MDR1 expression, which may promote radiosensitivity of NPC cells.