Ginsenoside Rd reverses cisplatin resistance in non-small-cell lung cancer A549 cells by downregulating the nuclear

Song Chian1, Yanna Zhao2, Ming Xu2

  • 1The Criminal Science and Technology Department, Zhejiang Police College.

Anti-Cancer Drugs
|August 16, 2019
PubMed

Insights

Ginsenoside Rd (GS-Rd) combats drug resistance in non-small-cell lung cancer (NSCLC) by inhibiting the NRF2 pathway. This research highlights NRF2 as a therapeutic target and ginseng compounds as potential treatments for NSCLC chemoresistance.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Clinical drug resistance to platinum-based chemotherapy hinders non-small-cell lung cancer (NSCLC) treatment.
  • The nuclear factor erythroid 2-related factor 2 (NRF2) pathway promotes cancer cell proliferation and chemoresistance.
  • Ginsenoside Rd (GS-Rd), a key ginsenoside component, exhibits anti-cancer properties.

Purpose of the Study:

  • To investigate the role of the NRF2 pathway in acquired chemoresistance in NSCLC.
  • To evaluate the efficacy of GS-Rd in overcoming drug resistance in NSCLC.
  • To explore GS-Rd's mechanism of action in sensitizing cancer cells to chemotherapy.

Main Methods:

  • Established cisplatin (DDP)-resistant A549 lung cancer cell lines (A549/DDP).
  • Assessed the effect of GS-Rd on cell proliferation, cell cycle, and drug sensitivity.
  • Investigated the modulation of the NRF2 pathway and its target genes by GS-Rd.
  • Utilized NRF2 knockdown to confirm its role in GS-Rd's synergistic effects.

Main Results:

  • GS-Rd inhibited A549 cell proliferation and induced G0/G1 phase arrest.
  • A549/DDP cells exhibited multidrug resistance, with activated NRF2 and associated proteins.
  • GS-Rd treatment downregulated the NRF2 pathway and sensitized A549/DDP cells to chemotherapy drugs.
  • NRF2 knockdown diminished the synergistic effects of GS-Rd, confirming NRF2's critical role.

Conclusions:

  • NRF2 is crucial in acquired drug resistance in NSCLC.
  • GS-Rd effectively overcomes chemoresistance by downregulating the NRF2 pathway.
  • The NRF2 pathway represents a promising therapeutic target for NSCLC, with ginseng compounds showing potential efficacy.

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