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Utilization of a UPLC-MS/MS Approach to Elucidate the Role of ABCB1-Mediated Paclitaxel Resistance in Non-Small Cell

Sha Hu1,2, Wenjing Wang1, Qianfang Hu3

  • 1Department of Pharmacy, Children's Hospital of Soochow University, Suzhou, 215025, China.

Oncology Research
|January 30, 2026
PubMed
Abstract

Insights

Paclitaxel resistance in non-small cell lung cancer is driven by ABCB1 (P-glycoprotein) efflux. Inhibiting ABCB1 resensitizes cancer cells to paclitaxel, offering a promising therapeutic strategy.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Acquired resistance to paclitaxel is a major challenge in non-small cell lung cancer (NSCLC) treatment.
  • Understanding the mechanisms of resistance is crucial for developing effective chemotherapy strategies.

Purpose of the Study:

  • To investigate the molecular mechanisms of paclitaxel resistance in NSCLC.
  • To explore strategies for overcoming paclitaxel resistance in NSCLC.

Main Methods:

  • Utilized a paclitaxel-resistant A549/TAX cell model.
  • Employed cell counting kit-8 (CCK-8) assay, colony formation, and apoptosis assays for viability assessment.
  • Conducted transcriptome profiling (RNA sequencing) and western blotting to identify molecular changes.
  • Quantified paclitaxel disposition using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).

Main Results:

  • A549/TAX cells showed significant paclitaxel resistance compared to parental cells.
  • ATP-binding cassette subfamily B member 1 (ABCB1), also known as P-glycoprotein, was significantly upregulated in resistant cells.
  • ABCB1 overexpression led to increased intracellular paclitaxel efflux, reducing its cytotoxic effect.
  • Genetic silencing or pharmacological inhibition of ABCB1 restored intracellular paclitaxel levels and decreased cell viability.

Conclusions:

  • ABCB1-mediated drug efflux is a key mechanism of paclitaxel resistance in NSCLC.
  • UPLC-MS/MS is a sensitive method for measuring paclitaxel concentration.
  • Inhibiting ABCB1 shows potential for resensitizing resistant NSCLC cells to paclitaxel therapy.
Keywords:
ATP-binding cassette subfamily B member 1 (ABCB1)Non-small cell lung cancer (NSCLC)chemoresistancepaclitaxelultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)

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