ABSTRACT
Objective@#The characteristics of T1 relaxation values and the expression levels of organic anion transport system (OATP) and multidrug resistance protein carrier (MRP) on hepatocyte surface membrane were quantitatively studied to evaluate liver function in normal C57BL/6 mice with gadoxetic disodium-enhanced MRI.@*Methods@#Ten 6-weeks-old, normal C57BL/6 mice were included in this study. Gadoxetic disodium- enhanced MRI examination was performed. Longitudinal relaxation time images before and 20 min after contrast injection (hepatobiliary-specific phase) were acquired. T1-relaxation time, T1 relaxation time decline rate (△T) and rapid initial enhancement slope percentage in the first-pass study of the liver parenchyma before and after administration of gadoxetate disodium were measured. Liver parenchyma specimens were detected by Western blotting and the values of OATP1, MRP2, and MRP3 were recorded. Statistical results were expressed in mean.@*Results@#The mean T1 relaxation time of 10 normal C57BL/6 mice before and after enhancement was 659.13 ± 24.07, and 408.87 ± 27.21 ms. The mean T1 relaxation time decline rate and rapid initial enhancement slope percentage in the first-pass study was 37.12% ± 4.95% and 4.14% ± 0.96% ms. Furthermore, the mean value of OATP1, MRP2 and MRP3 were 29 952.1 ± 11 475.2, 34 376.4 ± 33 228.4 and 357 308.9 ± 64 646.5.@*Conclusion@#T1-relaxation values, T1 relaxation time decline rate and rapid initial enhancement slope percentage in the first-pass study before and after gadoxetic disodium-enhanced MRI were determined in normal C57BL/6 mice as well as quantitative values of OATP1, MRP2 and MRP3 at the molecular level on the hepatocyte surface membrane were helpful for liver injury model with control study.
ABSTRACT
To investigate the effects of Gegen Qinlian decoction on the expression of P-glycoprotein (P-gp) and multi-drug resistance protein (MRP) in epithelial cells of human colon adenocarcinoma Caco-2 cells．The effects of different concentrations of Gegen Qinlian decoction on the expression levels of p-gp and MRP1-6 mRNA in Caco-2 cells were detected by real time quantitative reverse transcriptase PCR (qRT-PCR).12 h after drug treatment (5.00 g·L⁻¹), the expression levels of MDR1 and MRP1-6 were significantly down-regulated at concentration of 5.00 g·L⁻¹; the mRNA expression levels of MDR1，MRP1，MRP2，MRP4，MRP5 and MRP6 were significantly down-regulated at concentration of 2.50 g·L⁻¹; only the expression levels of MRP2 and MRP5 were significantly affected at concentration of 1.00 g·L⁻¹. The results showed that the expression levels of MDR1 and MRP1-6 mRNA in Caco-2 cells could be down-regulated in a dose-dependent manner. Gegen Qinlian decoction may reduce drug efflux by down-regulating the mRNA expression of cell transporters in Caco-2 cell, and increase the time of drug action, thereby enhancing the bioavailability of chemotherapeutic drugs.
ABSTRACT
Objective:To obesrve the influence of DNA-PKcs in the chemoresistance of multi-drug resistance malignant glioma cells,and to explore its molecuIar mechanism in chemoresistance.Methods:siRNA was used to construct the DNA-PKcs knockdown human glioma U251 cell line;Western blotting method was used to detect the expressions of DNA-PKcs in U251 cells (U251 cells), doxorubicin (ADM)resistant U251 cells (U251/ADM cells),DNA-PKcs knockdown and ADM resistant U251 cells (U251/ADM/siDNA-PKcs cells).CCK8 method was used to detect the cell proliferation activity in three groups;Western blotting method was used to detect the expressions of MDR1, pNF-κB/p6, total Akt, pAkt/T308 and pAKT/S473 in the cells in three groups. Results:The expression level of DNA-PKcs in U251/ADM cells was significantly higher than those in U251 cells and U251/ADM/siDNA-PKcs cells (P 0.05).Conclusion:DNA-PKcs can significantly enhance the chemoresistance of multi-drug resistance malignant glioma cells,the underlying mechanism is related to up-regulation of pAKT/S473,pNF-κB/p65 and MDR1 expressions.