Curcumin-loaded nanoparticles reversed radiotherapy-triggered enhancement of MDR1 expression of CNE-2 cells in nasopharyngeal carcinoma

Abstract

This study explored the effect of nanoparticle-encapsulating curcumin on strongly expressed multidrug resistance gene 1 (MDR1) in a human low-differentiated nasopharyngeal carcinoma cell line (CNE-2). The curcumin/chitosan-deoxycholic acid nanoparticles were prepared, and cells received different treatments: radiotherapy, empty carrier, curcumin and curcumin-loaded nanoparticles, followed by analysis of cell survival using the clonogenic assay, apoptosis, MDR1 and miR-593 level. Cell survival fractions in the curcumin group and curcumin-loaded nanoparticles group were reduced significantly. Moreover, we observed a reduced cell survival fraction in the curcumin-loaded nanoparticles group (p < 0.05). Remarkably, higher apoptosis rates were observed in cells receiving curcumin or curcumin-loaded nanoparticles treatments compared with radiotherapy. Moreover, the curcumin-loaded nanoparticle treatment enhanced apoptosis (p<0.05). Furthermore, a decreased MDR1 level was denoted in curcumin group and curcumin-loaded nanoparticles group and a further reduced MDR1 expression in nanoparticles group (p < 0.05). A higher miR-593 expression was observed in the curcumin group and curcumin-loaded nanoparticles group with a relative higher level in nanoparticles group (p<0.05). MDR1 expression in inhibitor group was significantly strengthened (p<0.05). Curcumin that is encapsulated in nanoparticles exhibited a stronger radio sensitizing effect. Its combination with radiotherapy can effectively inhibit NPC tumor growth, and suppress MDR1 expression while enhancing miR-593. After retarding the miR-593, the MDR1 expression was intensified. The radio sensitizing effect of curcumin-loaded nanoparticles was regulated by miR-593 but not triggered by MDR1. The curcumin-loaded nanoparticles mediated enhanced expression of miR-593, which in turn inhibited the transcription and translation of MDR1 gene, thereby reducing the radio resistance of NPC and restraining the growth of NPC more effectively.