Pulsatilla saponin D regulates ras-related C3 botulinum toxin substrate 3 (RAC3) to overcome resistance to paclitaxel in lung adenocarcinoma cells

BMC Cancer. 2024 Jan 10;24(1):55. doi: 10.1186/s12885-024-11841-6.

Abstract

Background: Paclitaxel, a tubulin-binding agent, is a Food and Drug Administration-approved first-line drug for the treatment of non-small cell lung cancer (NSCLC), for both squamous and non-squamous cell lung carcinoma, with paclitaxel/carboplatin + bevacizumab a common chemotherapy regimen for stage IV non-squamous NSCLC; however, primary or acquired resistance to paclitaxel is gradually increasing, leading to treatment failure.

Methods: Our results show that Ras-related C3 botulinum toxin substrate 3 (RAC3) is overexpressed in cultured paclitaxel-resistant cells and that RAC3 expression levels are negatively correlated with sensitivity of lung adenocarcinoma cells to paclitaxel. Pulsatilla saponin D could inhibit RAC3 expression, and we hypothesize that it may block paclitaxel resistance. Further, we found that treatment with paclitaxel combined with Pulsatilla saponin D, can overcome lung adenocarcinoma cell resistance to paclitaxel alone in cell culture and mouse xenograft models.

Keywords: Lung adenocarcinoma cell; Paclitaxel; Pulsatilla saponin D; RAC3; Resistance.

MeSH terms

  • Adenocarcinoma of Lung* / drug therapy
  • Animals
  • Botulinum Toxins*
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Disease Models, Animal
  • Humans
  • Lung Neoplasms* / drug therapy
  • Mice
  • Paclitaxel / pharmacology
  • Paclitaxel / therapeutic use
  • Saponins*
  • United States
  • rac GTP-Binding Proteins

Substances

  • Paclitaxel
  • Pulsatilla saponin D
  • Botulinum Toxins
  • RAC3 protein, human
  • rac GTP-Binding Proteins
  • Saponins