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从藏红花中提取的藏红花酸在化疗中对多重耐药表型发生率的影响。

The effects of crocetin, extracted from saffron, in chemotherapy against the incidence of multiple drug resistance phenotype.

作者信息

Neyshaburinezhad Navid, Hashemi Maryam, Ramezani Mohammad, Arabzadeh Sepideh, Behravan Javad, Kalalinia Fatemeh

机构信息

Biopharmaceutics and Pharmacokinetic Division, Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Iran J Basic Med Sci. 2018 Nov;21(11):1192-1197. doi: 10.22038/IJBMS.2018.29474.7118.

DOI:10.22038/IJBMS.2018.29474.7118
PMID:30483395
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6251388/
Abstract

OBJECTIVES

Crocetin, one of the main substances of saffron extract, has anti-cancer effects. Drug resistance proteins (e.g. MRP1 and MRP2) are important reasons for the failure of cancer therapy. We intended to investigate the efficacy of crocetin on MRP and MRP activity in human ovarian cisplatin-resistant carcinoma cell line (A2780-RCIS).

MATERIALS AND METHODS

The cytotoxic effect of crocetin was evaluated by the MTT assay. The efficacy of crocetin on MRP and MRP expression at mRNA level was studied by real-time RT-PCR. The effect of crocetin on the activity of MRP transporters was determined by drug efflux assay.

RESULTS

Crocetin decreased cell proliferation in the A2780 (IC: 183±7 µM) and A2780-RCIS (IC: 316±9 µM). Crocetin decreased the expression level of MRP1 (22±2 %) and MRP2 (48±8 %) in A2780-RCIS and inhibited MRP pumps function directly in A2780 (44±1 %) and A2780-RCIS (88±10 %) and indirectly in A2780 (32±2 %) and A2780-RCIS (48±15 %) respectively.

CONCLUSION

Our findings showed that crocetin could quench drug resistance through modulation of MRP transporters in the drug resistant human ovarian cancer cells.

摘要

目的

西红花苷是藏红花提取物的主要成分之一，具有抗癌作用。耐药蛋白（如MRP1和MRP2）是癌症治疗失败的重要原因。我们旨在研究西红花苷对人卵巢顺铂耐药癌细胞系（A2780-RCIS）中MRP及MRP活性的影响。

材料与方法

采用MTT法评估西红花苷的细胞毒性作用。通过实时RT-PCR研究西红花苷在mRNA水平对MRP及MRP表达的影响。采用药物外排试验测定西红花苷对MRP转运蛋白活性的影响。

结果

西红花苷降低了A2780（IC：183±7 μM）和A2780-RCIS（IC：316±9 μM）细胞的增殖。西红花苷降低了A2780-RCIS中MRP1（22±2%）和MRP2（48±8%）的表达水平，并分别直接抑制A2780（44±1%）和A2780-RCIS（88±10%）以及间接抑制A2780（32±2%）和A2780-RCIS（48±15%）中MRP泵的功能。

结论

我们的研究结果表明，西红花苷可通过调节耐药人卵巢癌细胞中的MRP转运蛋白来消除耐药性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bbf/6251388/94358c3be92d/IJBMS-21-1192-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bbf/6251388/0d1550f23dd4/IJBMS-21-1192-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bbf/6251388/e71a1c1c86ac/IJBMS-21-1192-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bbf/6251388/9ee2904df887/IJBMS-21-1192-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bbf/6251388/94358c3be92d/IJBMS-21-1192-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bbf/6251388/0d1550f23dd4/IJBMS-21-1192-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bbf/6251388/e71a1c1c86ac/IJBMS-21-1192-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bbf/6251388/9ee2904df887/IJBMS-21-1192-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bbf/6251388/94358c3be92d/IJBMS-21-1192-g004.jpg

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