Treatment of leukaemia cells with 3p-siRNA-MDR1 down-regulated MDR1 expression, reduced-drug resistance and induced immune and pro-apoptotic effects in drug-resistant HL-60/Adr and K562/Adr human leukaemia cell lines.
The cytotoxic studies have demonstrated a higher sensitivity of the leukemia lines to DOX-BNNPs compared with the carcinoma lines: IC<sub>50</sub>(DOX-BNNPs) is 1.13, 4.68, 0.025, and 0.14 μg/mL for the KB-3-1, MDR KB-8-5, K562, and MDR i-S9 cell lines, respectively.
In contrast, it had no effect on P-glycoprotein-mediated paclitaxel resistance in MDR1-transduced human leukemia K562 cells and multidrug resistance-related protein 1-mediated doxorubicin resistance in MRP1-transfected human epidermoid cancer KB-3-1 cells.
In conclusion, these results suggested that the MDR1 TT genotype might influence risk of development of acute lympoblastic leukemia and the CC genotype might be linked to a poor prognosis of ALL.
In the tumor-bearing nude mice, anti-tumor drugs vincristine, daunorubicin (DNR), STI571, and STI571 plus VCR for the treatment of mdr1 and bcr/abl double positive leukemia were studied respectively.
Expression dynamics of drug resistance genes, multidrug resistance 1 (MDR1) and lung resistance protein (LRP) during the evolution of overt leukemia in myelodysplastic syndromes.
These findings indicate that siRNA specifically and efficiently interferes with the expression of mdr1 and could be used as a molecularly defined therapeutic approach for MDR in the treatment of leukemia.
In this review, we cover the current information and postulate that epigenetic modification of MDR1 chromatin influences gene transcription in leukaemia.
P-glycoprotein (P-gp)/multi-drug resistance 1 (MDR1) gene is recognized to be, at least in part, responsible for the refractoriness to chemotherapy of leukemia.
To overcome P-gp-mediated drug resistance, we have developed six anti-MDR1 hammerhead ribozymes and delivered them to P-gp-overproducing human leukemia cell line by a retroviral vector containing RNA polymerase III promoter.
The MDR1 expression rate was significantly correlated with factors such as a history of preceding chemotherapy, elder age of the patient, and certain disease types (eg, leukemia progressed from myelodysplastic syndrome).
Although innumerable reports have been published in which P-gp has been shown to confer MDR to malignant (including leukemia) cells, so far, large-scale studies in the clinical setting have not convincingly proven that MDR1 plays a major role in clinical drug resistance when the influence of other known prognostic factors in human leukemia are taken into account.