Nilotinib enhances the efficacy of conventional chemotherapeutic drugs in CD34⁺CD38⁻ stem cells and ABC transporter overexpressing leukemia cells.

Incomplete chemotherapeutic eradication of leukemic CD34⁺CD38⁻ stem cells is likely to result in disease relapse. The purpose of this study was to evaluate the effect of nilotinib on eradicating leukemia stem cells and enhancing the efficacy of chemotherapeutic agents. Our results showed that ABCB1 and ABCG2 were preferentially expressed in leukemic CD34⁺CD38⁻ cells.

Euphorbia factor L1 reverses ABCB1-mediated multidrug resistance involving interaction with ABCB1 independent of ABCB1 downregualtion.

Euphorbia factor L1 (EFL1) belongs to diterpenoids of genus Euphorbia. In this article, its reversal activity against ABCB1-mediated MDR in KBv200 and MCF-7/adr cells was reported. However, EFL1 did not alter the sensitivity of KB and MCF-7 cells to chemotherapeutic agents.

Up-regulation of ABCB1/P-glycoprotein by escaping promoter hypermethylation indicates poor prognosis in hematologic malignancy patients with and without bone marrow transplantation.

We investigated the correlation between MDR1 promoter methylation status and MDR1 expression in 228 hematologic malignancies patients and 90 healthy controls. High level of MDR1 mRNA correlated to promoter hypomethylation and strongly associated with poor prognosis indicated by 2-year survival rates, poor CR rate (without BMT) and high relapse rate (with BMT). Furthermore, relative luciferase activity of methylated MDR1 at promoter -50 region was significantly higher than that of the unmethylated.

Lapatinib (Tykerb, GW572016) reverses multidrug resistance in cancer cells by inhibiting the activity of ATP-binding cassette subfamily B member 1 and G member 2.

Lapatinib is active at the ATP-binding site of tyrosine kinases that are associated with the human epidermal growth factor receptor (Her-1 or ErbB1) and Her-2. It is conceivable that lapatinib may inhibit the function of ATP-binding cassette (ABC) transporters by binding to their ATP-binding sites. The aim of this study was to investigate the ability of lapatinib to reverse tumor multidrug resistance (MDR) due to overexpression of ABC subfamily B member 1 (ABCB1) and ABC subfamily G member 2 (ABCG2) transporters.

[Advances in the study of expression and regulation of P-glycoprotein].

Resistance to the cytotoxic actions of antineoplastic drugs remains a barrier to the establishment of curative chemotherapy regimens for cancer. Over-expression of P-glycoprotein (P-gp), encoded by the MDR1 gene is the major molecular mechanism enhancing efflux pump for various anticancer agents, hence caused MDR. Transcription factor, DNA methylation, histone acetylation/deacetylation, phosphorylation and glycosylation and MDR1 gene polymorphisms play pivotal role in regulation of P-glycoprotein, and may become new therapeutic targets.