Matrine alkaloids modulating DNA damage repair in chemoresistant non-small cell lung cancer cells

BMC Cancer. 2024 Oct 16;24(1):1283. doi: 10.1186/s12885-024-12991-3.

Abstract

Background: Non-small cell lung cancer (NSCLC) presents a significant challenge in the medical field due to its high incidence and resistance to chemotherapy. Chemoresistance in NSCLC diminishes treatment efficacy and contributes to poor patient outcomes. Matrine alkaloids have shown promise in reversing chemotherapy resistance in NSCLC by targeting DNA repair mechanisms.

Methods: Utilizing molecular dynamics simulations, we explored the interactions between Matrine alkaloids and DNA repair-related proteins to elucidate their impact on NSCLC cells. In vitro experiments involved treating A549/DDP cells with Matrine alkaloids to evaluate their sensitizing effects on lung cancer cells. Additionally, animal model experiments were conducted to validate the therapeutic potential of Matrine alkaloids in NSCLC treatment.

Results: Our findings demonstrate that Matrine alkaloids disrupt DNA damage repair processes in NSCLC cells, leading to increased sensitivity to chemotherapy. Molecular docking studies revealed the intricate mechanisms by which Matrine alkaloids interact with DNA repair proteins, impacting cell survival and proliferation. Both cell experiments and animal models confirmed the chemosensitizing effects of Matrine alkaloids in NSCLC treatment.

Conclusion: Matrine alkaloids offer a promising avenue for overcoming chemotherapy resistance in NSCLC by interfering with DNA repair pathways. This study lays a solid foundation for future clinical investigations into the potential of Matrine alkaloids as effective therapeutic agents for enhancing NSCLC treatment outcomes.

Keywords: Chemotherapy sensitization; DNA repair; Matrine alkaloids; Molecular docking; NSCLC; Treatment strategy.

MeSH terms

  • A549 Cells
  • Alkaloids* / pharmacology
  • Animals
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / metabolism
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • DNA Damage* / drug effects
  • DNA Repair* / drug effects
  • Drug Resistance, Neoplasm* / drug effects
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / pathology
  • Matrines*
  • Mice
  • Molecular Docking Simulation*
  • Molecular Dynamics Simulation
  • Quinolizines* / pharmacology
  • Xenograft Model Antitumor Assays*

Substances

  • Alkaloids
  • Matrines
  • Quinolizines