MRP1 and its role in anticancer drug resistance

Lu, Jie; Pokharel, Deep; Bebawy, Mary

doi:10.3109/03602532.2015.1105253

Cited by 131 publications

(97 citation statements)

References 157 publications

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“…Previous studies have compiled numerous reports on the key role of MRP1 in MDR (15)(16)(17)27). In the present study, it was demonstrated that MRP1 is negatively regulated by miR-134, and that FOXM1 siRNA significantly downregulated MRP1 expression in lung adenocarcinoma cells.…”

Section: Discussionsupporting

confidence: 60%

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MicroRNA-134 reverses multidrug resistance in human lung adenocarcinoma cells by targeting FOXM1

Li¹,

Chen²,

Jin³

et al. 2017

Oncology Letters

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Abstract. Multidrug resistance (MDR) is the primary barrier to the success of chemotherapy for lung adenocarcinoma. MicroRNA (miR)-134, which is downregulated in lung adenocarcinoma, influences cell proliferation, apoptosis and invasion of lung adenocarcinoma. However, the function of miR-134 in the MDR of lung adenocarcinoma remains unclear. In the present study, it was identified that miR-134 expression is significantly downregulated in A549/cisplatin MDR lung adenocarcinoma cells, as compared with A549 parental cells. miR-134 regulates the sensitivity of lung adenocarcinoma cells to certain anticancer drugs. Furthermore, it was demonstrated that forkhead box M1 and multidrug resistance-associated protein 1 are functional targets of miR-134. These data revealed an important role for miR-134 in the regulation of MDR in lung adenocarcinoma.

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Section: Discussionsupporting

confidence: 60%

“…The alteration of MRP1 expression has previously been associated with certain lung diseases, and this protein may be pivotal in protecting the lungs via its ability to efflux an array of drugs to sub-lethal levels (26,27). Previous studies have compiled numerous reports on the key role of MRP1 in MDR (15)(16)(17)27).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-134 reverses multidrug resistance in human lung adenocarcinoma cells by targeting FOXM1

Li¹,

Chen²,

Jin³

et al. 2017

Oncology Letters

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“…63 Thus, the presence of a spiro-cyclopropyl substituent at the 4-position of the pyrrolidine ring has been found to contribute not only to enhancing potency and improving protein-adjusted EC 50 values, but also to a notable PK profile in monkeys ( Figure Figure 19. 66 To address this metabolic liability of 43, these investigators replaced the dimethylamino ethyl substituent at N 1 of the benzimidazole ring with the butyronitrile moiety and the bulky substituent at benzimidazolone ring with a small substituent (e.g., isopropyl) to yield compound 44, having 19 excellent antiviral potency and Caco-2 permeability as shown in Figure 19.…”

Section: Compound 38 (Simeprevir/olysio): Compound 38 (Tmc435/simeprementioning

confidence: 95%

The “Cyclopropyl Fragment” is a Versatile Player that Frequently Appears in Preclinical/Clinical Drug Molecules

2016

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Recently, there has been an increasing use of the cyclopropyl ring in drug development to transition drug candidates from the preclinical to clinical stage. Important features of the cyclopropane ring are, the (1) coplanarity of the three carbon atoms, (2) relatively shorter (1.51 Å) C-C bonds, (3) enhanced π-character of C-C bonds, and (4) C-H bonds are shorter and stronger than those in alkanes. The present review will focus on the contributions that a cyclopropyl ring makes to the properties of drugs containing it. Consequently, the cyclopropyl ring addresses multiple roadblocks that can occur during drug discovery such as (a) enhancing potency, (b) reducing off-target effects,

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“…Previous studies have found that higher MRP1 expression could confer MDR in various cancers including breast cancer [10,11]. For instance, enforced expression of MRP1 enhanced adriamycin (ADR) chemoresistance of prostate cancer cells [12].…”

Section: Introductionmentioning

confidence: 99%

Linc00518 Contributes to Multidrug Resistance Through Regulating the MiR-199a/MRP1 Axis in Breast Cancer

Chang

Zhou

et al. 2018

Cell Physiol Biochem

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Background/Aims: Long non-coding RNAs (LncRNAs) have been validated to be pivotal mediators in multidrug resistance (MDR) of various cancers. This study aims to explore the roles and molecular mechanisms of linc00518 implicated in chemoresistance in breast cancer. Methods: Expressions of linc00518, miR-199a and MRP1 were evaluated by RT-qPCR or western blot. IC 50 values of adriamycin (ADR), vincristine (VCR) and paclitaxel (PTX) were determined by XTT assays and cell apoptosis was assessed by flow cytometry. Luciferase reporter and RIP assays were employed to detect the interaction of linc00518, miR-199a and MRP-1. Results: linc00518 expression increased nearly 2 fold and MRP1 level elevated about 2.5 fold in breast cancer tissues as compared to that in adjacent normal tissues. Also, almost 2 fold upregulation of linc00518 and MRP-1 expressions was observed in MCF-7 cells than in MCF-10A cells. Additionally, linc00518 level was almost 2.5 fold higher and MRP1 level was about 2 fold increased in ADR-resistant MCF-7 cells (MCF-7/ADR) than in parental cell line MCF-7. Linc00518 knockdown enhanced chemosensitivity to ADR, VCR and PTX, and boosted ADR-, VCR-and PTX-induced apoptosis in MCF-7/ADR cells. miR-199a inhibitor conferred chemoresistance to ADR, VCR and PTX in MCF-7/ADR cells, and suppressing miR-199a reversed multi-drug susceptibility induced by linc00518 knockdown. Furthermore, linc00518 could act as a molecular sponge of miR-199a to repress MRP1 expression. MRP1 depletion increased the sensitivity of MCF-7/ADR cells to ADR, VCR and PTX, and this effect was attenuated following miR-199a inhibition or linc00518 overexpression. Also, linc00518 silencing increased ADRmediated anti-tumor effect in vivo. Conclusions: linc00518 downregulation reduced MDR by regulating miR-199a/MRP1 axis in breast cancer.

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MRP1 and its role in anticancer drug resistance

Cited by 131 publications

References 157 publications

MicroRNA-134 reverses multidrug resistance in human lung adenocarcinoma cells by targeting FOXM1

MicroRNA-134 reverses multidrug resistance in human lung adenocarcinoma cells by targeting FOXM1

The “Cyclopropyl Fragment” is a Versatile Player that Frequently Appears in Preclinical/Clinical Drug Molecules

Linc00518 Contributes to Multidrug Resistance Through Regulating the MiR-199a/MRP1 Axis in Breast Cancer

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