Tumor cells may display a multidrug resistance phenotype by overexpression of ATP binding cassette transporter genes such as multidrug resistance (MDR) 1 P-glycoprotein (P-gp) or the multidrug resistance protein 1 (MRP1). MDR3 P-gp is a close homologue of MDR1 P-gp, but its role in MDR is probably minor and remains to be established. The MRP1 protein belongs to a family of at least six members....

The phenomenon of multidrug resistance implies that a wide spectrum of structurally and functionally unrelated chemotherapeutic drugs are recognized and processed by the molecular system which protects multidrug-resistant (MDR) cells against lipophilic cytotoxic drugs. This suggests that lipophilic agents with low toxicity may also be recognized and processed by this molecular system. At high c...

We have established preclinical models for the development of drug resistance to vincristine (a major drug used in the treatment of pediatric rhabdomyosarcoma) using cell lines. The RD cell line has a mutant P53 phenotype and does not have detectable P-glycoprotein (P-gp) or multidrug resistance-related protein (MRP) despite expressing low levels of mdr-1 mRNA, which encodes P-gp and mrp1 mRNA....

Multidrug resistance (MDR) is one of the major obstacles in successful chemotherapy. The combination of chemotherapy drugs and multidrug-resistant reversing agents for treating MDR tumor is a good strategy to overcome MDR. In this work, we prepared the simple redox-responsive micelles based on mPEG-SS-C18 as a co-delivery system to load the paclitaxel (PTX) and dasatinib (DAS) for treatment of ...

Chemoresistance is one of the main obstacles to successful cancer therapy and is frequently associated with multidrug resistance (MDR). One of the most studied mechanisms of MDR is the high expression of ATP-binding cassette (ABC) transporters. Here, we demonstrated that NP-1250, an ABCG2 inhibitor, induced apoptotic cell death in ABCG2-overexpres...

No control cell line was available for previous RNA interference studies on reversal of multidrug resistance (MDR) in colon cancer cells. Here, human COLO 320DM, with HT-29 as the control, colon cancer cell lines were used to investigate the reversal of MDR1/P-gp-dependent MDR by siRNA (#4123 and #4029 MDR1 siRNAs) targeting to MDR1 mRNA. Both siRNAs inhibited expression of MDR1 and P-gp in COL...

The ability of tumor cells to develop simultaneous resistance to structurally different cytotoxic drugs constitutes a major problem in cancer chemotherapy. It was previously demonstrated that multidrug-resistant Chinese hamster cell lines contain an amplified, transcriptionally active DNA sequence designated mdr. This report presents evidence that multidrug-resistant sublines of human KB carcin...

Chronic lymphocytic leukemia (CLL) is characterized by an often indolent course with a poor therapeutic response at advanced stage. We investigated the expression of the human multidrug resistance genes mdr, and mdr, in 31 patients with CLL. Using specific probes for mdr, and mdr, mRNA, respectively, expression of both genes could be found in 29 of 31 patients. Of those, nine had high expressio...

The screening of two different retroviral cDNA expression libraries to select genes that confer constitutive doxorubicin resistance has in both cases resulted in the isolation of the heat shock factor 1 (HSF1) transcription factor. We show that HSF1 induces a multidrug resistance phenotype that occurs in the absence of heat shock or cellular stress and is mediated at least in part through the c...