Using cell lines expressing high levels of endogenous MRP1 from three difficult to treat cancer types-lung cancer, ovarian cancer and high-risk neuroblastoma-we showed that the MRP1 modulator substantially lowered intracellular GSH levels as a single agent.
These data suggest that NBT can sensitize ADR-induced cytotoxicity against A549/ADR cells by inhibiting MRP1 expression, indicating that NBT could serve as an effective adjuvant agent for ADR-based chemotherapy in lung cancer.
The Novel Triazolonaphthalimide Derivative LSS-11 Synergizes the Anti-Proliferative Effect of Paclitaxel via STAT3-Dependent MDR1 and MRP1 Downregulation in Chemoresistant Lung Cancer Cells.
Two different MRP1 overexpressing cell lines were used, the doxorubicin-selected human lung cancer cell line H69 AR and the transfected Madin-Darby Canine Kidney cell line MDCK II MRP1.
We reviewed characteristic resistance mechanisms in lung cancer including over-expression of ATP-binding cassette (ABC) transporters P-glycoprotein and structural, functional or expression alterations of β-tubulin (βII, βIII, βIV) which may devote to the development of acquired resistance to the Vinca alkaloids; multidrug-resistance proteins (MRP1, MRP2, MRP3) and RLIP76 protein have also been identified that probably play a significant role in intrinsic resistance.
In conclusion, the Arg723Gln (2168G > A) polymorphism of ABCC1 appears to be a potential susceptibility marker for lung cancer in the Chinese population, especially in older people.
After cytological confirmation of lung cancer type, total RNA was extracted from biopsy samples and reverse transcribed to cDNA, and real-time PCR for the genes of interest [P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), breast cancer resistance protein (BCRP), lung resistance protein (LRP) and topoisomerase IIα (TOPIIα)], was performed.
The genotyping analyses for 6 common regulatory variants (reference single-nucleotide polymorphism 4728709 [rs4728709] and rs2188524 in the 5' flanking region of ABCB1 and rs3842 in its 3' untranslated region; rs3743527, rs212090, and rs212091 in the 3' untranslated region of ABCC1) was conducted in a case-control study of 500 patients with incident lung cancer and 517 cancer-free controls in a Chinese population.
These results reemphasize the important role of MRP-1/CD9 and KAI1/CD82 in the suppression of the metastatic process and also show the feasibility of gene therapy when using these tetraspanins for lung cancer to prevent metastasis to the regional lymph nodes.
The use of celecoxib for adjuvant therapy in lung cancer patients may contribute to their decreased resistance to chemotherapeutic drugs transported by MRP1.
In most lung cancers, this resistance is associated with the overexpression of (a) multidrug resistance-associated protein (MRP) responsible for drug efflux from the cancer cells (pump resistance) and (b) BCL2 protein that activates antiapoptotic cellular defense (nonpump resistance).
To investigate the roles played by the multidrug resistance-associated protein (MRP1) homologues MRP3 and MRP4 in resistance to platinum drugs, we examined steady-state levels of mRNA for both MRP3 and MRP4 in normal lung and lung cancer specimens as well as peripheral mononuclear cells (PMN) after platinum drug exposure.
To investigate the role of the multidrug resistance-associated protein (MRP1) homologue MRP5 in relation to platinum drug resistance, we examined the steady-state levels of the mRNAs for MRP5 in both lung cancer cell lines and peripheral mononuclear cells (PMN) after exposure to platinum drug and in normal lung and lung cancer tissue specimens.
Multidrug resistance-associated protein (MRP) mRNA expression and drug sensitivity in lung cancer cells were examined, and the effects of verapamil, a modulating agent for MRP, on drug sensitivity were also tested.
Expression of gamma-glutamylcysteine synthetase (gamma-GCS) and multidrug resistance-associated protein (MRP), but not human canalicular multispecific organic anion transporter (cMOAT), genes correlates with exposure of human lung cancers to platinum drugs.
To this end, we took advantage of the fact that the overexpression of MDR1 and MRP genes, two genes known to be associated with the development of drug resistance, is very common in lung cancer.
The multidrug resistance-associated protein (MRP), mediating a multidrug resistance (MDR) phenotype, has been reported to be overexpressed in several drug-selected lung cancer cell lines.
This set of observations suggests that assessment of the expression status of KAI1/CD82 and MRP-1/CD9 by tumors may provide prognostic information on the clinical behavior of lung cancer.
In conclusion, we have shown that a human revertant lung cancer cell line (COR-L23/Rev) has the ability to recover quickly, similar levels of MRP expression and resistance as COR-L23/R after a transient exposure to the MDR-drugs doxorubicin and vincristine.
Using an RNase protection assay we have analyzed the expression of MRP in non-Pgp MDR sublines of the human lung cancer cell lines SW-1573 (non-small cell lung cancer) and GLC4 (small cell lung cancer).