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Synergistic Effect of HAD-B1 and Osimertinib Against Gefitinib Resistant HCC827 Non-Small Cell Lung Cancer Cells
Eun-Ju Ko1, Eun-Bin Kwag2, Ji-Hye Park3
1Cha Ilsan Medical Center of Cha University, Ilsan, Republic of Korea.
Abstract:
In this study, we investigated the synergistic effect of co-administration of osimertinib and HAD-B1 using gefitinib-resistant non-small cell lung cancer cells, HCC827-GR. HAD-B1 is composed of 4 natural drugs, Panax Notoginseng Radix, Panax ginseng C. A. Meyer, Cordyceps militaris, and Boswellia carterii Birdwood, and has been reported to have therapeutic effects on patients with advanced non-small cell lung cancer in several studies. Resistance to gefitinib in HCC827 cells was acquired through MET activity. Co-treatment with osimertinib and HAD-B1 reduced the cell viability of HCC827-GR cells. In addition, phosphorylation of MET and ERK were effectively suppressed for HCC827-GR cells. And, compared to when osimertinib and HAD-B1 were administered alone, cell proliferation was significantly inhibited and apoptosis was effectively induced when osimertinib and HAD-B1 were co-administered to HCC827-GR cells. We found that the synergistic effect of osimertinib and HAD-B1 combination therapy resulted in cancer cell death and cell cycle arrest by targeting the ERK and mTOR signaling pathways. In conclusion, this study confirmed that the combination of osimertinib, a third-generation anticancer drug, and HAD-B1, a natural anticancer drug, had a potentially synergistic effect on non-small cell lung cancer resistant to EGFR-targeted anticancer drugs.
Insights
This study shows that combining osimertinib with HAD-B1, a natural drug complex, synergistically inhibits gefitinib-resistant non-small cell lung cancer. The combination therapy effectively reduces cancer cell viability and induces apoptosis by targeting key signaling pathways.
Area of Science:
- Oncology
- Pharmacology
- Natural Products
Background:
- Non-small cell lung cancer (NSCLC) often develops resistance to targeted therapies like gefitinib.
- MET activity is implicated in acquired resistance to EGFR inhibitors in NSCLC.
- HAD-B1, a natural compound, has shown therapeutic potential in advanced NSCLC.
Purpose of the Study:
- To investigate the synergistic effect of co-administering osimertinib and HAD-B1 in gefitinib-resistant NSCLC cells.
- To elucidate the molecular mechanisms underlying the combination therapy's efficacy.
Main Methods:
- Utilized gefitinib-resistant NSCLC cell line (HCC827-GR).
- Assessed cell viability, proliferation, and apoptosis.
- Analyzed the phosphorylation status of MET and ERK signaling pathways.
- Investigated the impact on ERK and mTOR signaling pathways.
Main Results:
- Co-treatment with osimertinib and HAD-B1 significantly reduced HCC827-GR cell viability.
- The combination therapy effectively suppressed MET and ERK phosphorylation.
- Osimertinib and HAD-B1 combination demonstrated enhanced inhibition of cell proliferation and induced apoptosis compared to monotherapy.
- Synergistic effects were linked to targeting of ERK and mTOR signaling pathways.
Conclusions:
- The combination of osimertinib and HAD-B1 exhibits a potentially synergistic effect against EGFR-targeted drug-resistant NSCLC.
- This combination therapy offers a promising strategy for overcoming resistance in NSCLC treatment.
- Targeting ERK and mTOR pathways is crucial for the observed synergistic anti-cancer effects.
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