Mahdizadeh Shadi, Karimi Gholamreza, Behravan Javad, Arabzadeh Sepideh, Lage Hermann, Kalalinia Fatemeh
Department of Cell and Molecular Biology, Kish International Campus, University of Tehran, Kish, Iran.
Medical Toxicology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Daru. 2016 Jun 24;24(1):17. doi: 10.1186/s40199-016-0155-8.
Crocin, one of the main constituents of saffron extract, has numerous biological effects such as anti-cancer effects. Multidrug resistance-associated proteins 1 and 2 (MRP1 and MRP2) are important elements in the failure of cancer chemotherapy. In this study we aimed to evaluate the effects of crocin on MRP1 and MRP2 expression and function in human ovarian cancer cell line A2780 and its cisplatin-resistant derivative A2780/RCIS cells.
The cytotoxicity of crocin was assessed by the MTT assay. The effects of crocin on the MRP1 and MRP2 mRNA expression and function were assessed by real-time RT-PCR and MTT assays, respectively.
Our study indicated that crocin reduced cell proliferation in a dose-dependent manner in which the reduction in proliferation rate was more noticeable in the A2780 cell line compared to A2780/RCIS. Crocin reduced MRP1 and MRP2 gene expression at the mRNA level in A2780/RCIS cells. It increased doxorubicin cytotoxicity on the resistant A2780/RCIS cells in comparison with the drug-sensitive A2780 cells.
Totally, these results indicated that crocin could suppress drug resistance via down regulation of MRP transporters in the human ovarian cancer resistant cell line.
藏红花提取物的主要成分之一藏红花素具有多种生物学效应，如抗癌作用。多药耐药相关蛋白1和2（MRP1和MRP2）是癌症化疗失败的重要因素。在本研究中，我们旨在评估藏红花素对人卵巢癌细胞系A2780及其顺铂耐药衍生物A2780/RCIS细胞中MRP1和MRP2表达及功能的影响。
采用MTT法评估藏红花素的细胞毒性。分别通过实时RT-PCR和MTT法评估藏红花素对MRP1和MRP2 mRNA表达及功能的影响。
我们的研究表明，藏红花素以剂量依赖的方式降低细胞增殖，其中与A2780/RCIS相比，A2780细胞系的增殖率降低更为明显。藏红花素降低了A2780/RCIS细胞中MRP1和MRP2基因在mRNA水平的表达。与药物敏感的A2780细胞相比，它增加了阿霉素对耐药的A2780/RCIS细胞的细胞毒性。
总的来说，这些结果表明藏红花素可通过下调人卵巢癌耐药细胞系中MRP转运蛋白来抑制耐药性。
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