Abstract
Background: Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has been the major bottleneck that limits the long-term clinical efficacy. Therefore, the exploration of novel strategies for the treatment of non-small cell lung cancer (NSCLC) is urgent. Sijunzi Tang (SJZ) has been usually used as a complementary therapy for cancer patients that can prolong their overall life. Nevertheless, its underlying mechanism when combined with EGFR-TKIs is not clear. Methods: Here, the anti-tumor activity was evaluated by determining cell viability by using the Cell Counting Kit-8 (CCK-8). A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was established to simultaneously quantify nine metabolites in the glutamine metabolic pathway, such as glutamine, glutamate, αketoglutaric acid, fumarate, succinate, citrate, cis-aconitate, alanine, and malate in PC-9/GR cells. Results: The results showed that SJZ could enhance the sensitivity of lung cancer cells to gefitinib. The content of glutamine and glutamate in the SJZ/gefitinib group was significantly lower than that in the gefitinib group, while the concentration of other metabolites did not change significantly. Conclusion: In summary, SJZ can reverse gefitinib resistance by modulating glutamine metabolism. Our results suggested that SJZ might be a potential resistance reversal herbal medicine and combined with gefitinib might be a promising strategy for the therapy of lung cancer. Also, the research will provide novel insights for the study of the mechanisms on Traditional Chinese medicine (TCM) prescriptions-reversed resistance of EGFR-TKIs, and scientific basis for the combined treatment of lung cancer with TCM and EGFR-TKIs.
Sijunzi Tang Enhances The Sensitivity of Lung Cancer Cells To Gefitinib Based On Glutamine Metabolism