P-glycoprotein(P-gp)is an ATP-dependent efflux transporter that is distributed in many tissues and organs.P-gp can selectively pump endogenous substrates and exogenous chemicals from the cell to the outside of the cell to maintain a stable endo-environment.However,it meanwhile restricts the entry of therapeutic drug into tissues and organs,and in particular,mediates the multidrug resistance of tumor cells to chemotherapeutic drugs.Therefore,understanding the localization of P-gp in different tissues and organs may be an important breakthrough point for disease treatment.In this paper,we mainly review the molecular structure,transport mechanism,localization,and regulation of P-gp in different tissues and organs,providing reference for the subsequent treatment of diseases.
Humans ; ATP Binding Cassette Transporter, Subfamily B, Member 1/chemistry* ; Animals ; Drug Resistance, Multiple

OBJECTIVE: To analyze the mdr-1 gene promoter methylation and histone acetylation status in both MCF-7/Adr and MCF-7 cells and to preliminarily explore the epigenetic mechanism of multidrug resistance in breast cancer. METHODS: mdr-1 gene promoter methylation status of the 2 cell lines was detected by methylation-sensitive PCR. mRNA expression of DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) was detected by real-time quantitative PCR. Acetylation level of histone H3 and H4 was examined by optical density assay. RESULTS: Promoter hypermethylation of mdr-1 gene was observed in MCF-7 cells whereas hypomethylation was found in MCF-7/Adr cells. Expression of DNMT1, DNMT3a, and DNMT3b mRNA in MCF-7/Adr cells significantly decreased compared with that of MCF-7 cells (P<0.05). H3 and H4 histone acetylation levels of MCF-7/Adr cells were obviously higher than those of the MCF-7 cells (P<0.01). Expression of HDAC1, HDAC2, HDAC7, and Sirtuin type 1 (SIRT1) mRNA in MCF-7/Adr cells was significantly reduced (P<0.05). CONCLUSION Hypomethylation of the promoter region of mdr-1 gene, high H3 and H4 histone acetylation, and low mRNA expression of DNMTs and HDACs may be important epigenetic factors for the development of MDR in MCF-7/ Adr cells.
ATP Binding Cassette Transporter, Subfamily B, Member 1 ; genetics ; Acetylation ; Breast Neoplasms ; pathology ; Cell Line, Tumor ; DNA (Cytosine-5-)-Methyltransferase 1 ; DNA (Cytosine-5-)-Methyltransferases ; genetics ; metabolism ; DNA Methylation ; genetics ; Drug Resistance, Multiple ; genetics ; Drug Resistance, Neoplasm ; genetics ; Epigenesis, Genetic ; Female ; Histone Deacetylases ; genetics ; metabolism ; Histones ; chemistry ; Humans ; Promoter Regions, Genetic ; genetics ; RNA, Messenger ; genetics ; metabolism