期刊
MOLECULAR BIOLOGY REPORTS
卷 46, 期 6, 页码 6525-6532出版社
SPRINGER
DOI: 10.1007/s11033-019-05098-7
关键词
A2780; A2780-RCIS; Crocetin; Ovarian cancer cell line; PLGA-crocetin nanoparticles
资金
- Mashhad University of Medical Sciences [931570]
- Biotechnology Research Center
- Research Council of Mashhad University of Medical Sciences, Iran
Nanoparticles and herbal medicines have gained considerable attention in overcoming multidrug resistance through different mechanisms. In this study, the effects of poly (Lactic-co-glycolic acid)-crocetin nanoparticles (PLGA-Crt NPs) on MRP1 and MRP2 activity in a human ovarian cisplatin-resistant carcinoma cell line (A2780-RCIS) and its parental form (A2780) were evaluated. PLGA-Crt NPs were formulated and then characterized. The cytotoxic effect of Crt, PLGA-Crt NPs, and empty PLGA NPs was assessed using MTT test in A2780 and A2780-RCIS cells. The effect of PLGA-Crt NPs on MRP1 and MRP2 mRNA expression was evaluated by Real-Time qRT-PCR. The impact of PLGA-Crt NPs on the functioning of MRP transporters was assessed by the doxorubicin efflux assay. The particle size, entrapment efficiency (EE) and loading capacity (LC) of PLGA-Crt NPs were obtained about 239.8 +/- 9 nm, 79 +/- 3% and 4.9 +/- 0.2%, respectively. The PLGA-Crt NPs IC50 values were obtained 104 +/- 3 mu M and 96 +/- 2 mu M in A2780 and A2780-RCIS cell lines, respectively. The Real-time RT-PCR results demonstrated the inhibition of mRNA expression of MRP2 in all studied concentrations (up to 67 +/- 8% at 100 mu M) in A2780-RCIS cells. PLGA-Crt NPs showed more indirect efflux inhibition (up to 70 +/- 5%) compared to direct inhibition (up to 49 +/- 5%). The encapsulation of crocetin into PLGA NPs can increase its inhibitory effects on drug resistance by downregulating MRP2 transporters.
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