Multidrug resistance strength of the novel multidrug resistance gene HA117: compared with MRP1

Zhao, Lihua; Sun, Yue; Li, Xiaoqing; Jin, Xianqing; You-hua, XU; Guo, Zhenhua; Liang, Rui; Ding, Xionghui; Chen, Ting-Fu; Wang, Siqi

doi:10.1007/s12032-010-9624-y

Cited by 3 publications

(2 citation statements)

References 23 publications

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“…The inhibition ratio of tumor cells at each drug concentration was calculated using the following formula: Inhibition ratio (%) = (1 -average OD value of the experimental cells/average OD value of the control cells) x 100. The half inhibiting concentration (IC 50 ) of each chemotherapeutic drug was determined from the inhibition ratio for each concentration (15).…”

Section: Analysis Of the Optimum Irradiation Of Reversing Mdr Of Sk-nmentioning

confidence: 99%

Study of the mechanisms underlying the reversal of multidrug resistance of human neuroblastoma multidrug-resistant cell line SK-N-SH/MDR1 by low-intensity pulsed ultrasound

et al. 2013

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Abstract. The aim of the present study was to investigate the underlying mechanism(s) involved in reversing multidrug resistance (MDR) of SK-N-SH/MDR1 by low-intensity pulsed ultrasound (LIPUS). Membrane alteration of SK-N-SH/ MDR1 cells exposed to LIPUS was analyzed by scanning electron microscopy (SEM). Immunofluorescence and western blotting were used\ to detect changes in the expression of the MDR-related proteins P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1) and glutathione-S-transferase-π (GST-π) after the optimum ultrasonic. The optimum ultrasonic conditions were 0.3 MHz, 1.0 W/cm 2 , 40 sec and the chemosensitivity of SK-N-SH/MDR1 cells was significantly increased (P<0.05). The optimum ultrasonic-induced perforation of the irradiated cell membranes was observed by SEM. The expression of P-gp was significantly decreased in the group treated by optimum ultrasonic (P<0.05), but not the expressions of MRP1 or GST-π (P>0.05). We demonstrated that LIPUS effectively reverses the MDR of SK-N-SH/MDR1, presumably via augmenting membrane permeability and decreasing the P-gp expression of SK-N-SH/MDR1.

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Section: Analysis Of the Optimum Irradiation Of Reversing Mdr Of Sk-nmentioning

confidence: 99%

Study of the mechanisms underlying the reversal of multidrug resistance of human neuroblastoma multidrug-resistant cell line SK-N-SH/MDR1 by low-intensity pulsed ultrasound

et al. 2013

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“…This type of cells also forms tumorspheres with elevated expression of CD44 high /CD24 low phenotype [38] but shows mixed multidrug resistance of MDR and MRP types [39,40]. Therefore the kinetics of MDR efflux was measured with universal MDR substrate calcein [41] using cell array slides (Molecular Cytomics Inc., Boston, MA [42]), otherwise experimental protocol was similar to that used with MCF-7 cells.…”

Section: Resultsmentioning

confidence: 99%

Kinetics of MDR Transport in Tumor-Initiating Cells

2013

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Multidrug resistance (MDR) driven by ABC (ATP binding cassette) membrane transporters is one of the major causes of treatment failure in human malignancy. MDR capacity is thought to be unevenly distributed among tumor cells, with higher capacity residing in tumor-initiating cells (TIC) (though opposite finding are occasionally reported). Functional evidence for enhanced MDR of TICs was previously provided using a “side population” assay. This assay estimates MDR capacity by a single parameter - cell’s ability to retain fluorescent MDR substrate, so that cells with high MDR capacity (“side population”) demonstrate low substrate retention. In the present work MDR in TICs was investigated in greater detail using a kinetic approach, which monitors MDR efflux from single cells. Analysis of kinetic traces obtained allowed for the estimation of both the velocity (V max) and affinity (K M) of MDR transport in single cells. In this way it was shown that activation of MDR in TICs occurs in two ways: through the increase of V max in one fraction of cells, and through decrease of K M in another fraction. In addition, kinetic data showed that heterogeneity of MDR parameters in TICs significantly exceeds that of bulk cells. Potential consequences of these findings for chemotherapy are discussed.

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Combined QSAR and molecule docking studies on predicting P-glycoprotein inhibitors

Tan

Mei

et al. 2013

J Comput Aided Mol Des

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P-glycoprotein (P-gp) is an ATP-binding cassette multidrug transporter. The over expression of P-gp leads to the development of multidrug resistance (MDR), which is a major obstacle to effective treatment of cancer. Thus, designing effective P-gp inhibitors has an extremely important role in the overcoming MDR. In this paper, both ligand-based quantitative structure-activity relationship (QSAR) and receptor-based molecular docking are used to predict P-gp inhibitors. The results show that each method achieves good prediction performance. According to the results of tenfold cross-validation, an optimal linear SVM model with only three descriptors is established on 857 training samples, of which the overall accuracy (Acc), sensitivity, specificity, and Matthews correlation coefficient are 0.840, 0.873, 0.813, and 0.683, respectively. The SVM model is further validated by 418 test samples with the overall Acc of 0.868. Based on a homology model of human P-gp established, Surflex-dock is also performed to give binding free energy-based evaluations with the overall accuracies of 0.823 for the test set. Furthermore, a consensus evaluation is also performed by using these two methods. Both QSAR and molecular docking studies indicate that molecular volume, hydrophobicity and aromaticity are three dominant factors influencing the inhibitory activities.

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Multidrug resistance strength of the novel multidrug resistance gene HA117: compared with MRP1

Cited by 3 publications

References 23 publications

Study of the mechanisms underlying the reversal of multidrug resistance of human neuroblastoma multidrug-resistant cell line SK-N-SH/MDR1 by low-intensity pulsed ultrasound

Study of the mechanisms underlying the reversal of multidrug resistance of human neuroblastoma multidrug-resistant cell line SK-N-SH/MDR1 by low-intensity pulsed ultrasound

Kinetics of MDR Transport in Tumor-Initiating Cells

Combined QSAR and molecule docking studies on predicting P-glycoprotein inhibitors

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