scholarly journals Nuclear Multidrug-Resistance Related Protein 1 Contributes to Multidrug-Resistance of Mucoepidermoid Carcinoma Mainly via Regulating Multidrug-Resistance Protein 1: A Human Mucoepidermoid Carcinoma Cells Model and Spearman's Rank Correlation Analysis

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e69611 ◽  
Author(s):  
Bolei Cai ◽  
Ye Miao ◽  
Yuan Liu ◽  
Xiaofang Xu ◽  
Sumin Guan ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Mucoepidermoid Carcinoma ◽  
Rank Correlation ◽  
Carcinoma Cells ◽  
Multidrug Resistance Protein ◽  
Related Protein ◽  
Multidrug Resistance Protein 1 ◽  
Spearman’S Rank Correlation ◽  
Resistance Protein ◽  
Multidrug Resistance Related Protein

scholarly journals Multidrug resistance protein 1 regulates lipid asymmetry in erythrocyte membranes

2000 ◽  
Vol 350 (2) ◽  
pp. 531-535 ◽  
Author(s):  
David W. C. DEKKERS ◽  
Paul COMFURIUS ◽  
Rein G. J. VAN GOOL ◽  
Edouard M. BEVERS ◽  
Robert F. A. ZWAAL
Keyword(s):  
Multidrug Resistance ◽  
Erythrocyte Membrane ◽  
Erythrocyte Membranes ◽  
Multidrug Resistance Protein ◽  
Multidrug Resistance Protein 1 ◽  
Lipid Asymmetry ◽  
Appreciable Change ◽  
Outer Leaflet ◽  
Resistance Protein ◽  
Phospholipid Distribution

The role of multidrug resistance protein 1 (MRP1) in the maintenance of transbilayer lipid asymmetry in the erythrocyte membrane was investigated. The transbilayer distribution of endogenous phospholipids and [(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]hexanoyl (NBD)-labelled lipid analogues was compared in the absence and the presence of inhibitors of MRP1. At equilibrium the transbilayer distribution of the NBD analogues (in the absence of MRP1 inhibitors) was very similar to that of the endogenous lipids. Inhibition of MRP1 by verapamil or indomethacin resulted in a shift in the amount of probe that was internalized: approx. 50% of NBD-labelled phosphatidylcholine (PtdCho) and 9% of NBD-sphingomyelin (NBD-Spm) were no longer extractable by BSA in cells treated with inhibitor, in comparison with 25% and 3% for control cells respectively. To verify whether inhibition of MRP1 also affected the distribution of the endogenous phospholipids, phospholipase A2 and sphingomyelinase were used to assess the amount of each of the various lipid classes present in the membrane outer leaflet. No shift in phospholipid distribution was observed after 5h of incubation with verapamil or indomethacin. However, after 48h of incubation with these inhibitors, significantly smaller amounts of PtdCho and Spm were present in the outer membrane leaflet. No appreciable change was observed in the distribution of phosphatidylethanolamine or phosphatidylserine. Decreased hydrolysis of PtdCho and Spm was not due to endovesicle formation, as revealed by electron microscopy. This is the first report to show that MRP1 has a role in the maintenance of the outwards orientation of endogenous choline-containing phospholipids in the erythrocyte membrane.

scholarly journals MiR-331-3p Links to Drug Resistance of Pancreatic Cancer Cells by Activating WNT/β-Catenin Signal via ST7L

2020 ◽  
Vol 19 ◽  
pp. 153303382094580
Author(s):  
Ting Zhan ◽  
Xiaoli Chen ◽  
Xia Tian ◽  
Zheng Han ◽  
Meng Liu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Drug Resistance ◽  
Multidrug Resistance ◽  
Cancer Cells ◽  
Breast Cancer Resistance Protein ◽  
Cancer Resistance ◽  
Multidrug Resistance Protein 1 ◽  
Pancreatic Cancer Cells ◽  
Resistance Protein ◽  
Multidrug Resistance Related Protein

Background: Pancreatic cancer is an aggressive type of cancer with poor prognosis, short survival rate, and high mortality. Drug resistance is a major cause of treatment failure in the disease. MiR-331-3p has been reported to play an important role in several cancers. We previously showed that miR-331-3p is upregulated in pancreatic cancer and promotes pancreatic cancer cell proliferation and epithelial-to-mesenchymal transition–mediated metastasis by targeting ST7L. However, it is uncertain whether miR-331-3p is involved in drug resistance. Methods: We investigated the relationship between miR-331-3p and pancreatic cancer drug resistance. As part of this, microRNA mimics or inhibitors were transfected into pancreatic cancer cells. Quantitative polymerase chain reaction was used to detect miR-331-3p expression, and flow cytometry was used to detect cell apoptosis. The Cell Counting Kit-8 assay was used to measure the IC50 values of gemcitabine in pancreatic cancer cells. The expression of multidrug resistance protein 1, multidrug resistance-related protein 1, breast cancer resistance protein, β-Catenin, c-Myc, Cyclin D1, Bcl-2, and Caspase-3 was evaluated by Western blotting. Results: We confirmed that miR-331-3p is upregulated in gemcitabine-treated pancreatic cancer cells and plasma from chemotherapy patients. We also confirmed that miR-331-3p inhibition decreased drug resistance by regulating cell apoptosis and multidrug resistance protein 1, multidrug resistance-related protein 1, and breast cancer resistance protein expression in pancreatic cancer cells, whereas miR-331-3p overexpression had the opposite effect. We further demonstrated that miR-331-3p effects in drug resistance were partially reversed by ST7L overexpression. In addition, overexpression of miR-331-3p activated Wnt/β-catenin signaling in pancreatic cancer cells, and ST7L overexpression restored activation of Wnt/β-catenin signaling. Conclusions: Taken together, our data demonstrate that miR-331-3p contributes to drug resistance by activating Wnt/β-catenin signaling via ST7L in pancreatic cancer cells. These data provide a theoretical basis for new targeted therapies in the future.

scholarly journals Expansion of a Specific Plasmodium falciparum PfMDR1 Haplotype in Southeast Asia with Increased Substrate Transport

mBio ◽  
2020 ◽  
Vol 11 (6) ◽  
Author(s):  
Carla Calçada ◽  
Miguel Silva ◽  
Vitória Baptista ◽  
Vandana Thathy ◽  
Rita Silva-Pedrosa ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Multidrug Resistance ◽  
Southeast Asia ◽  
Gene Copy ◽  
Multidrug Resistance Protein ◽  
Combination Therapies ◽  
Transport Capacity ◽  
Multidrug Resistance Protein 1 ◽  
Content Type ◽  
Resistance Protein

ABSTRACT Artemisinin-based combination therapies (ACTs) have been vital in reducing malaria mortality rates since the 2000s. Their efficacy, however, is threatened by the emergence and spread of artemisinin resistance in Southeast Asia. The Plasmodium falciparum multidrug resistance protein 1 (PfMDR1) transporter plays a central role in parasite resistance to ACT partner drugs through gene copy number variations (CNV) and/or single nucleotide polymorphisms (SNPs). Using genomic epidemiology, we show that multiple pfmdr1 copies encoding the N86 and 184F haplotype are prevalent across Southeast Asia. Applying genome editing tools on the Southeast Asian Dd2 strain and using a surrogate assay to measure transporter activity in infected red blood cells, we demonstrate that parasites harboring multicopy N86/184F PfMDR1 have a higher Fluo-4 transport capacity compared with those expressing the wild-type N86/Y184 haplotype. Multicopy N86/184F PfMDR1 is also associated with decreased parasite susceptibility to lumefantrine. These findings provide evidence of the geographic selection and expansion of specific multicopy PfMDR1 haplotypes associated with multidrug resistance in Southeast Asia. IMPORTANCE Global efforts to eliminate malaria depend on the continued success of artemisinin-based combination therapies (ACTs) that target Plasmodium asexual blood-stage parasites. Resistance to ACTs, however, has emerged, creating the need to define the underlying mechanisms. Mutations in the P. falciparum multidrug resistance protein 1 (PfMDR1) transporter constitute an important determinant of resistance. Applying gene editing tools combined with an analysis of a public database containing thousands of parasite genomes, we show geographic selection and expansion of a pfmdr1 gene amplification encoding the N86/184F haplotype in Southeast Asia. Parasites expressing this PfMDR1 variant possess a higher transport capacity that modulates their responses to antimalarials. These data could help tailor and optimize antimalarial drug usage in different regions where malaria is endemic by taking into account the regional prevalence of pfmdr1 polymorphisms.

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