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

To improve the antisense activity of AS ODN (antisense oligodeoxynucleotide), a conjugate covalently linked to DOX (doxorubicin) at its 3'-end was synthesized and its antisense activity in human carcinoma DOX-resistant cells (KB-A-1) was investigated in vitro. The intracellular DOX concentration in KB-A-1 cells treated with the conjugate was detected in vitro by HPLC. Results showed that the intracellular DOX concentration was 6.4-fold higher in KB-A-1 cells treated with the conjugate when compared with that in the cells treated with DOX alone. In contrast, a 1.8-fold increase in the concentration of DOX was observed when the cells were treated with AS ODN. Reverse transcriptase PCR and Western-blot analysis showed a more significant decrease in the amount of mdr1 (multidrug resistance 1 gene) mRNA and P-glycoprotein in KB-A-1 cells. Chemosensitivity of KB-A-1 cells to DOX was also investigated in vitro. When the cells were first exposed to the conjugate (0.5 microM) for 24 h and then exposed to DOX for 24 h, the IC(50) value of DOX decreased from 21.5 to 2.2 microM, whereas the IC(50) value of DOX decreased only to 16.8 microM when the cells were treated with the mixture of the same concentration of AS ODN. These results suggest that the conjugate is effective in reversing multidrug resistance. Further studies will be conducted to explore the effect of the conjugate on tumours in vivo.
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PMID:Inhibition of P-glycoprotein and increasing of drug-sensitivity of a human carcinoma cell line (KB-A-1) by an antisense oligodeoxynucleotide-doxorubicin conjugate in vitro. 1520 36

The aim of this study was to examine the effect and mechanism of green tea polyphenols (TP) on reversal of multidrug resistance (MDR) in a carcinoma cell line. Using the MTT assay, TP was examined for its modulating effects on the drug-resistant KB-A-1 cells and drug-sensitive KB-3-1 cells. When 10 microg mL(-1) (-)-epigallocatechin gallate (EGCG) or 40 microg mL(-1) TP were present simultaneously with doxorubicin (DOX), the IC50 of DOX on KB-A-1 cells decreased from 10.3 +/- 0.9 microg mL(-1) to 4.2 +/- 0.2 and 2.0 +/- 0.1 microg mL(-1), respectively. TP and EGCG enhanced the DOX cytotoxicity on KB-A-1 cells by 5.2- and 2.5-times, respectively, but did not show a modulating effect on KB-3-1 cells. This indicated that both TP and EGCG had reversal effects on the MDR phenotype in-vitro. A KB-A-1 cell xenograft model was established, and the effect of TP on reversing MDR in-vivo was determined. Mechanistic experiments were conducted to examine the uptake, efflux and accumulation of DOX. Cloning and expression of the nucleotide binding domain of the human MDR1 gene in Escherichia coli was established, and by using colorimetry to examine the activity of ATPase to hydrolyse ATP, the ATPase activity of target nucleotide binding domain protein was determined. TP exerted its reversal effects through the inhibition of ATPase activity, influencing the function of P-glycoprotein, and causing a decreased extrusion of anticancer drug and an increased accumulation of anticancer drug in drug resistant cells. Using reverse transcription-polymerase chain reaction, the inhibitory effect of TP on MDR1 gene expression was investigated. Down-regulation of MDR1 gene expression was the main effect, which resulted in the reversal effect of TP on the MDR phenotype. TP is a potent MDR modulator with potential in the treatment of P-glycoprotein mediated MDR cancers.
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PMID:Reversal of cancer multidrug resistance by green tea polyphenols. 1548 46

A conjugate of antisense oligodeoxynucleotide (AS ODN) covalently linked with deoxorubicin (DOX) was synthesized. Its properties and antitumour activity in human carcinoma DOX resistant cells (KB-A-1) were investigated in vitro. The results showed that the conjugate was strongly stable both in Dulbecco's Phosphate-Buffered Saline (PBS) and in culture medium. The intracellular concentration of the conjugate was higher than that of the AS DON by HPLC analysis. The conjugate showed potent dose-dependent inhibition to the growth of KB-A-1 cells. Chemosensitivity of KB-A-1 cells to DOX was also investigated in vitro. When the cells were first exposed to the conjugate (0.5 microM) and then exposed to DOX for 24 h, the IC50 value of DOX decreased from 21.5 to 2.2 microM. In contrast, when treated with the mixture of the same concentration of the AS ODN with equivalent DOX, the IC50 value of DOX was 16.8 microM. Intracellular DOX concentration was detected in KB-A-1 treatment with the conjugate in vitro by HPLC. The results showed that the intracellular DOX concentration was 6.4-fold increased in KB-A-1 cells treated with the conjugate compared to treatment with DOX alone. In contrast, 1.8-fold increasing was observed when treated with the AS ODN. Western blot analysis showed a significantly decrease in the amount of P-glycoprotein in KB-A-1 cells. These results suggest that the conjugate is effective in reversing multidrug resistance. Certainly, further studies are conducting to explore the antitumour effect of the conjugate in vivo.
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PMID:In vitro reversal MDR of human carcinoma cell line by an antisense oligodeoxynucleotide-doxorubicin conjugate. 1551 10

Self-assembled phospholipid bilayer Nanodiscs have become an important and versatile tool among model membrane systems to functionally reconstitute membrane proteins. Nanodiscs consist of lipid domains encased within an engineered derivative of apolipoprotein A-1 scaffold proteins, which can be tailored to yield homogeneous preparations of disks with different diameters, and with epitope tags for exploitation in various purification strategies. A critical aspect of the self-assembly of target membranes into Nanodiscs lies in the optimization of the lipid:protein ratio. Here we describe strategies for performing this optimization and provide examples for reconstituting bacteriorhodopsin as a trimer, rhodopsin, and functionally active P-glycoprotein. Together, these demonstrate the versatility of Nanodisc technology for preparing monodisperse samples of membrane proteins of wide-ranging structure.
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PMID:Chapter 11 - Reconstitution of membrane proteins in phospholipid bilayer nanodiscs. 1990 57