Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Over-expression of MDR1 confers multidrug resistance (MDR) in cancers and remains a major cause for the failure of chemotherapy. In the present study, we found that V-Ets erythroblastosis virus E26 oncogene homolog 2 (ETS2) could activate MDR1 transcription and P-glycoprotein (P-gp) expression in SGC7901 cells. Knockdown of ETS2 attenuated MDR1 transcription and P-gp expression, and increased the sensitivity of MDR cancer cells to cytotoxic drugs that were transported by P-gp in SGC7901/VCR cells. ETS2 could bind to the ETS2 sites on the MDR1 promoter and activate its transcription. The regulation of MDR1 expression by ETS2 may provide potential ways to overcome MDR in cancer treatment.
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PMID:Involvement of V-Ets erythroblastosis virus E26 oncogene homolog 2 in regulation of transcription activity of MDR1 gene. 2281 65

Multidrug resistance (MDR), as one of the main problems in clinical breast cancer chemotherapy, is closely related with the over expression of drug efflux transporter P-glycoprotein (P-gp). In this study, a novel drug-loaded nanosystem was developed for inhibiting the P-gp expression and reversing MDR by multiplexed gene silencing, which composes of graphene oxide (GO) modified with two molecular beacons (MBs) and Doxorubicin (Dox). When the nanosystem was uptaken by the MDR breast cancer cells, Dox was released in the acidic endosomes and MBs were hybridized with target sequences. The intracellular multidrug resistance 1 (MDR1) mRNA and upstream erythroblastosis virus E26 oncogene homolog 1 (ETS1) mRNA can be silenced by MBs, which can effectively inhibit the expression of P-gp and further prevent the efflux of Dox and reverse MDR. In vitro and in vivo studies indicated that the strategy of reversing MDR by multiplexed gene silencing could obviously increase MCF-7/Adr cells' Dox accumulation and enormously enhance the therapeutic efficacy of MDR breast cancer chemotherapy.
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PMID:Reversing Multidrug Resistance by Multiplexed Gene Silencing for Enhanced Breast Cancer Chemotherapy. 2966 7