[NF-kappaB regulating expression of mdr1 gene and P-gp to reverse drug-resistance in leukemic cells]

Related Experiment Video

Updated: Jul 10, 2026

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
10:09

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

Yi Wang1, Xin Liu, Hai-Tao Zhang

  • 1Department of Hematology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710061, China.

Zhongguo Shi Yan Xue Ye Xue Za Zhi
|October 25, 2007
PubMed

Insights

Inhibiting NF-kappaB (nuclear factor kappa B) reduces drug resistance in hematologic malignant cells by decreasing P-glycoprotein (P-gp) and mdr1 expression, offering a new treatment strategy for leukemia.

Area of Science:

  • Hematology
  • Molecular Biology
  • Cancer Research

Background:

  • Hematologic malignant cells often develop drug resistance.
  • Nuclear factor kappa B (NF-kappaB) plays a role in anti-apoptotic mechanisms.
  • P-glycoprotein (P-gp) and mdr1 are key mediators of multidrug resistance.

Purpose of the Study:

  • To investigate the role of mdr1 in NF-kappaB-regulated anti-apoptosis in hematologic malignant cells.
  • To explore the potential of inhibiting NF-kappaB to reverse drug resistance.
  • To identify novel therapeutic strategies for refractory leukemia.

Main Methods:

  • Immunohistochemistry and computerized picture analysis to detect NF-kappaB activity and P-gp expression.
  • Reverse transcription-polymerase chain reaction (RT-PCR) to detect mdr1 expression.
  • Analysis of the relationship between NF-kappaB, P-gp, and mdr1 in K562/A02 cells treated with PDTC.

Main Results:

  • NF-kappaB/p65 expression was positively correlated with P-gp and mdr1 expression in a concentration- and time-dependent manner.
  • Inhibition of NF-kappaB led to reduced expression of mdr1 mRNA and P-gp.
  • Reduced mdr1 and P-gp expression enhanced the sensitivity of hematologic malignant cells to chemotherapy.

Conclusions:

  • NF-kappaB regulates anti-apoptosis in K562/A02 cells through the expression of mdr1 and P-gp.
  • Inhibiting NF-kappaB is a viable strategy to overcome drug resistance in hematologic malignancies.
  • Targeting the NF-kappaB pathway offers a promising approach for treating refractory leukemia.

More Related Videos

Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype14:51

Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype

Published on: June 17, 2022

Related Concept Videos

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters01:16

Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters

The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.