Crocin suppresses multidrug resistance in MRP overexpressing ovarian cancer cell line

被引:38
作者
Mahdizadeh, Shadi [1 ]
Karimi, Gholamreza [2 ]
Behravan, Javad [3 ,4 ]
Arabzadeh, Sepideh [3 ]
Lage, Hermann [5 ]
Kalalinia, Fatemeh [3 ,6 ]
机构
[1] Univ Tehran, Dept Cell & Mol Biol, Kish Int Campus, Kish, Iran
[2] Mashhad Univ Med Sci, Med Toxicol Res Ctr, Sch Pharm, Mashhad, Iran
[3] Mashhad Univ Med Sci, Biotechnol Res Ctr, Sch Pharm, POB 91775-1365, Mashhad, Iran
[4] Mashhad Univ Med Sci, Dept Pharmaceut Biotechnol, Sch Pharm, Mashhad, Iran
[5] Charite, Inst Pathol, Campus Mitte, D-13353 Berlin, Germany
[6] Mashhad Univ Med Sci, Med Genet Res Ctr, Mashhad, Iran
关键词
Crocin; Multidrug resistance; MRP1; MRP2; A2780; A2780/RCIS; DRUG-RESISTANCE; ABC-TRANSPORTERS; MECHANISMS; SAFFRON; CHEMOTHERAPY; CONSTITUENT; INHIBITION; PROTEINS; CROCETIN; REVERSAL;
D O I
10.1186/s40199-016-0155-8
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Background: 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. Methods: 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. Results: 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. Conclusion: Totally, these results indicated that crocin could suppress drug resistance via down regulation of MRP transporters in the human ovarian cancer resistant cell line.
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页数:8
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