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Characterization of in vitro Mrp2 transporter model based on intestinal organoids

Lei Zhang1, Chenmeizi Liang2, Peipei Xu2

  • 1East China Normal University and Shanghai Fengxian District Central Hospital Joint Research Center for Translational Medicine, Shanghai Key laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China; Department of Pharmacy, Shanghai Fengxian District Central Hospital, Shanghai, China.

Regulatory Toxicology and Pharmacology : RTP
|August 27, 2019
PubMed

Insights

A novel mouse intestinal organoid model effectively detects Multidrug resistance associated protein 2 (MRP2) function. This method aids in screening MRP2 inhibitors to combat multidrug resistance in cancer therapy.

Area of Science:

  • Pharmacology
  • Drug Discovery
  • Molecular Biology

Background:

  • Multidrug resistance associated protein 2 (MRP2) is crucial for drug disposition and interactions.
  • Understanding MRP2 function is vital for drug discovery and overcoming cancer multidrug resistance.

Purpose of the Study:

  • To establish a rapid and sensitive method for detecting MRP2 function using mouse intestinal organoids.
  • To validate the utility of this model for studying MRP2-mediated drug transport.

Main Methods:

  • Mouse intestinal crypts were cultured to form 3D organoids.
  • Organoids were characterized for their physiological structure relevant to MRP2 transport.
  • MRP2-mediated transport of a fluorescent substrate (CDF) was assessed using inhibitors (MK-571, probenecid).

Main Results:

  • The 3D intestinal organoids exhibited a suitable physiological structure for MRP2-mediated transport.
  • Inhibitors MK-571 and probenecid significantly reduced CDF accumulation, confirming MRP2 activity.
  • The model demonstrated rapid and effective detection of MRP2-mediated drug transport.

Conclusions:

  • A novel intestinal organoid model was successfully developed for studying MRP2 function.
  • This model provides a valuable tool for screening MRP2 inhibitors and understanding drug transport.
  • The findings support the use of organoids in drug discovery and overcoming multidrug resistance.
Keywords:
Drug transportIntestinal organoidsMouseMultidrug resistance-associated protein 2 (Mrp2)Transporter model

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