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Paeoniae radix overcomes resistance to EGFR-TKIs via aurora B pathway suppression in lung adenocarcinoma

Heerim Yeo1, Haeseung Lee2, Sang-Min Park1

  • 1College of Pharmacy, Chungnam National University, Republic of Korea.

Life Sciences
|October 3, 2024
PubMed

Insights

Paeoniae Radix (PR) combined with EGFR-TKIs may overcome lung adenocarcinoma resistance. This natural product suppresses the Aurora B pathway, enhancing apoptosis and drug response in EGFR-mutant LUAD.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Epidermal growth factor receptor (EGFR) inhibitors have improved outcomes for EGFR-mutant lung adenocarcinoma (LUAD).
  • Drug resistance to EGFR inhibitors remains a significant clinical challenge, limiting treatment efficacy.
  • Natural products offer potential avenues for overcoming therapeutic resistance.

Purpose of the Study:

  • To investigate the synergistic effects of Paeoniae Radix (PR) combined with first-generation EGFR-tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib.
  • To explore the potential of PR in overcoming acquired resistance to EGFR-TKIs in LUAD.
  • To elucidate the molecular mechanisms underlying the combined therapeutic effects.

Main Methods:

  • Transcriptomic analysis of EGFR-mutant LUAD cell lines treated with PR.
  • Experimental validation of PR combined with erlotinib and gefitinib.
  • Assessment of Aurora kinase activity and apoptosis induction.
  • Gene expression analysis to confirm pathway modulation.

Main Results:

  • PR treatment reversed gene signatures associated with EGFR-TKI resistance.
  • PR suppressed the Aurora B pathway, a key mediator of resistance.
  • Combination therapy enhanced LUAD cell responsiveness to erlotinib and gefitinib.
  • Inhibition of Aurora kinase activity and induction of apoptosis were observed.
  • Gene expression confirmed Aurora B pathway suppression and apoptotic pathway upregulation.

Conclusions:

  • Paeoniae Radix shows synergistic effects with EGFR-TKIs in overcoming LUAD resistance.
  • The combination therapy targets the Aurora B pathway and promotes apoptosis.
  • PR represents a promising natural product for developing novel therapeutic strategies against EGFR-TKI resistance in LUAD.
Keywords:
Combination therapyDrug resistanceHerbal medicineLung adenocarcinomaNatural productTranscriptome

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