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Trps1 is associated with the multidrug resistance of osteosarcoma by regulating MDR1 gene expression

Ming Jia1, Jing Hu1, Weiwei Li1

  • 1Department of Pathology and Pathophysiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China.

FEBS Letters
|February 5, 2014
PubMed

Insights

The transcription factor Trps1 regulates multidrug resistance (MDR) in osteosarcoma by controlling MDR1/P-gp expression. Inhibiting Trps1 reduces MDR1/P-gp, enhancing chemotherapy effectiveness.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Multidrug resistance (MDR) poses a significant challenge in osteosarcoma chemotherapy.
  • MDR is associated with the overexpression of drug-efflux transporters like MDR1/P-glycoprotein (P-gp).

Purpose of the Study:

  • To investigate the role of the transcription factor Trps1 in regulating MDR1/P-gp expression in osteosarcoma.
  • To explore the potential of targeting Trps1 for overcoming MDR in osteosarcoma treatment.

Main Methods:

  • Inhibition and overexpression of Trps1 in osteosarcoma cells.
  • Flow cytometry to assess drug accumulation.
  • Immunohistochemistry to analyze Trps1 and MDR1/P-gp expression in clinical samples.
  • Analysis of Trps1 binding to the MDR1 promoter and its effect on TGFbeta-1.

Main Results:

  • Trps1 inhibition repressed MDR1/P-gp expression, while Trps1 overexpression upregulated it.
  • Trps1 facilitated the efflux of anti-cancer drugs, reducing their intracellular accumulation.
  • Clinical osteosarcoma samples showed a direct correlation between Trps1 expression and MDR1/P-gp levels.
  • Trps1 was found to inhibit TGFbeta-1 and bind directly to the MDR1 promoter.

Conclusions:

  • Trps1 plays a crucial role in regulating MDR1 expression in osteosarcoma.
  • Trps1 represents a potential therapeutic target for overcoming multidrug resistance in osteosarcoma.
Keywords:
CHIPChemotherapyMDR1Multidrug resistanceOsteosarcomaP-gpTGFbeta-1TRPS1

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