Related Experiment Video

Updated: Apr 24, 2026

Methods to Discover Alternative Promoter Usage and Transcriptional Regulation of Murine Bcrp1
11:02

Methods to Discover Alternative Promoter Usage and Transcriptional Regulation of Murine Bcrp1

Published on: May 27, 2016

7.6K

Expression of ABCB6 is related to resistance to 5-FU, SN-38 and vincristine

Kentaro Minami1, Youhei Kamijo2, Yukihiko Nishizawa1

  • 1Department of Molecular Oncology, Kagoshima University, Kagoshima, Japan Department of Clinical Pharmacy and Pharmacology, Kagoshima University, Kagoshima, Japan.

Anticancer Research
|September 10, 2014
PubMed

Insights

The ATP-binding cassette (ABC) transporter ABCB6 contributes to multidrug resistance in cancer cells. This study shows ABCB6 enhances resistance to specific anticancer drugs like 5-fluorouracil, SN-38, and vincristine.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Drug Resistance Mechanisms

Background:

  • The KAS cell line exhibits resistance to both arsenite and multiple anticancer drugs.
  • Understanding the molecular basis of this multidrug resistance is crucial for developing effective cancer therapies.
  • ATP-binding cassette (ABC) transporters are frequently implicated in drug resistance phenotypes.

Purpose of the Study:

  • To identify the specific ABC transporters responsible for the multidrug resistance in KAS cells.
  • To elucidate the role of ABCB6 in the drug resistance profile of KAS cells.
  • To investigate the functional significance of ABCB6 in mediating resistance to various anticancer agents.

Main Methods:

  • Expression analysis of ABC transporters in KAS cells, focusing on ABCB6 and ABCC1/MRP1.
  • Generation of KB cells overexpressing ABCB6.
  • Generation of KAS cells with downregulated ABCB6 expression (knockdown).
  • Assessment of cellular sensitivity to arsenite, 5-fluorouracil (5-FU), SN-38, and vincristine (Vcr) in engineered cell lines.

Main Results:

  • Increased expression of ABCB6 and ABCC1/MRP1 was observed in KAS cells.
  • ABCB6 overexpression in KB cells conferred resistance to 5-FU, SN-38, and Vcr, but not to arsenite.
  • Downregulation of ABCB6 in KAS cells led to increased sensitivity to 5-FU, SN-38, and Vcr, without affecting arsenite sensitivity.

Conclusions:

  • ABCB6 plays a significant role in mediating resistance to 5-fluorouracil, SN-38, and vincristine.
  • ABCB6 is a key determinant of the multidrug resistance phenotype observed in KAS cells for these specific agents.
  • Targeting ABCB6 may represent a potential strategy to overcome resistance to these anticancer drugs.
Keywords:
ABC transportersABCB6anticancer agentsarsenitedrug resistance

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

2.7K
Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer06:21

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer

Published on: May 10, 2024

1.6K

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...
80
ABC Transporters: Exporter01:31

ABC Transporters: Exporter

ATP-binding cassette or ABC transporter is the largest superfamily of integral membrane proteins. The transporters have transmembrane-binding domains (TMDs) and nucleotide-binding domains (NBDs). The TMDs are specific to their substrates, whereas the NBDs are similar to engines that complete ATP hydrolysis to complete the substrate transport. They can be full transporters consisting of two TMDs and NBDs, half transporters with one TMD and NBD, while some encoded with a single TMD or NBD are...
5.7K
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...
2.6K
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...
4.9K
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...
186
ABC Transporters: Importer01:27

ABC Transporters: Importer

ATP-binding cassette or ABC transporters are a class of ATP-driven pumps that hydrolyze ATP to move solutes across the membrane. They can be grouped into importers and exporters. While exporters are present in all domains of life, importers exist only in bacteria and some plants.
In bacteria, based on the number of transmembrane helices and the chemical nature of their substrates, the ABC importers can be divided into three types:
2.6K