Curcumin-loaded nanoparticles reversed radiotherapy-triggered enhancement of MDR1 expression of CNE-2 cells in nasopharyngeal carcinoma
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摘要: 目的 本研究将探讨纳米颗粒包封姜黄素对人低分化鼻咽癌细胞系(CNE-2)中强表达多药耐药基因1(multidrug resistance gene 1，MDR1)的影响。 方法 制备姜黄素/壳聚糖-脱氧胆酸纳米颗粒，鼻咽癌细胞接受单纯放疗、空载体、姜黄素和负载姜黄素纳米颗粒的不同处理，然后使用克隆生成测定、细胞凋亡、MDR1和miR-593水平分析细胞存活率。 结果 姜黄素组和负载姜黄素纳米颗粒组的细胞存活分数显著降低。与放疗比较，在接受姜黄素或姜黄素负载纳米颗粒处理的细胞中观察到更高的细胞凋亡率。姜黄素组和负载姜黄素的纳米颗粒组的MDR1水平降低，纳米颗粒组中MDR1表达进一步降低(P＜0.05)。在姜黄素组和负载姜黄素的纳米颗粒组中观察到较高的miR-593表达，并且在纳米颗粒组中观察到相对较高的水平(P＜0.05)。包裹在纳米颗粒中的姜黄素表现出更强的放疗敏化作用。其与放疗合用可有效抑制鼻咽癌肿瘤生长，抑制MDR1表达，同时增强miR-593。在抑制miR-593后，MDR1表达增强。负载姜黄素的纳米颗粒的放射敏化作用由miR-593调节，但不受MDR1触发。 结论 负载姜黄素的纳米颗粒介导了miR-593的表达增强，进而抑制了MDR1基因的转录和翻译，从而降低了鼻咽癌的放疗抵抗，更有效地抑制了鼻咽癌的生长。
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关键词:
- 负载姜黄素的纳米颗粒 /
- 鼻咽癌 /
- 多药耐药基因1 /
- miR-593 /
- CNE-2细胞
Abstract: Objective This study explored the effect of nanoparticle-encapsulated curcumin on the highly expressed multidrug resistance gene 1 (MDR1) in a human low-differentiated nasopharyngeal carcinoma cell line (CNE2). Methods Curcumin/chitosan deoxycholic acid nanoparticles were prepared, and the cells were subjected to different treatments: radiotherapy, empty carriers, curcumin, and curcumin-loaded nanoparticles. Cell survival was analyzed using the clonogenic assay, and assessments of apoptosis, MDR1 levels, and miR593 levels were conducted. Results The cell survival fractions in the curcumin group and the curcumin-loaded nanoparticles group were significantly reduced. Notably, higher apoptosis rates were observed in cells treated with curcumin or curcumin-loaded nanoparticles compared to those that received only radiotherapy. Moreover, a decreased MDR1 level was noted in both the curcumin group and the curcumin-loaded nanoparticles group, with further reduction in MDR1 expression observed in the nanoparticle group (P < 0.05). Enhanced expression of miR593 was found in the curcumin group and the curcumin-loaded nanoparticles group, with a relatively higher level in the nanoparticle group (P < 0.05). Curcumin encapsulated in nanoparticles exhibited a stronger radiosensitizing effect. The combination of curcumin and radiotherapy effectively inhibited nasopharyngeal carcinoma (NPC) tumor growth, suppressed MDR1 expression, and enhanced miR593 levels. After inhibiting miR593, MDR1 expression increased. The radiosensitizing effect of curcumin-loaded nanoparticles was regulated by miR593 rather than being triggered by MDR1. Conclusion Curcumin-loaded nanoparticles mediated enhanced expression of miR593, which in turn inhibited the transcription and translation of the MDR1 gene, thereby reducing the radioresistance of NPC and effectively restraining its growth.-
Key words:
- curcumin-loaded nanoparticles /
- nasopharyngeal carcinoma /
- MDR1 /
- miR-593 /
- CNE-2 Cells
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表 1 引物序列
引物 序列 miR-593 正向引物：TGTCTCTGCTGGGGTTTCT 反向引物：GTGCAGGGTCCGAGGTATT U6 正向引物：CTCGCTTCGGCAGCACA 反向引物：AACGCTTCACGAATTTGCGT 
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