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Anti-Nuclear Antibody Screening Using HEp-2 Cells
Published on: June 23, 2014
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.
Abstract:
Clinical drug resistance to platinum-based chemotherapy is considered a major impediment in the successful treatment of non-small-cell lung cancer (NSCLC). The nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway regulates the oxidative stress response, and in many cancer types, the high constitutive expression of NRF2 leads to proliferation and chemoresistance. Ginsenoside Rd (GS-Rd) is the main active component of ginsenosides. Here, GS-Rd was found to inhibit the proliferation of A549 lung cancer cells and induce G0/G1 phase arrest. We established cisplatin (DDP)-resistant A549 cell lines (A549/DDP). The half maximal inhibitory concentrations of DDP, gemcitabine, and adriamycin were much higher in A549/DDP cells than in A549 cells. The A549/DDP cell lines developed multidrug resistance, accompanied by activation of multidrug resistance protein 1 and multidrug resistance-associated protein 1, as well as NRF2 and its target genes. Treatment with GS-Rd inhibited the NRF2 pathway and significantly sensitized A549/DDP cells to therapeutic drugs. In addition, NRF2 knockdown attenuated the synergistic effects of GS-Rd in both A549 and A54/DDP cells. Taken together, these data show that NRF2 plays an important role in acquired drug resistance in NSCLC, and GS-Rd may ameliorate this chemoresistance by downregulating the NRF2 pathway. This study demonstrates that the NRF2 pathway may serve as a therapeutic target in NSCLC, and ginseng compounds may be effective for the treatment of this disease.
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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