ABSTRACT
Non-small-cell lung cancer (NSCLC) remains the most common malignancy with the highest morbidity and mortality worldwide. In our previous study, we found that a classic traditional Chinese medicine (TCM) formula Ze-Qi-Tang (ZQT), which has been used in the treatment of respiratory diseases for thousands of years, could directly inhibit the growth of human NSCLC cells via the p53 signaling pathway. In this study, we explored the immunomodulatory functions of ZQT. We found that ZQT significantly prolonged the survival of orthotopic lung cancer model mice by modulating the tumor microenvironment (TME). ZQT remarkably reduced the number of MDSCs (especially G-MDSCs) and inhibited their immunosuppressive activity by inducing apoptosis in these cells via the STAT3/S100A9/Bcl-2/caspase-3 signaling pathway. When G-MDSCs were depleted, the survival promotion effect of ZQT and its inhibitory effect on lung luminescence signal disappeared in tumor-bearing mice. This is the first study to illustrate the immunomodulatory effect of ZQT in NSCLC and the underlying molecular mechanism.
Subject(s)
Apoptosis/drug effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Drugs, Chinese Herbal/pharmacology , Granulocytes/drug effects , Lung Neoplasms/drug therapy , Medicine, Chinese Traditional , Myeloid-Derived Suppressor Cells/drug effects , Animals , Calgranulin B/physiology , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Caspase 3/physiology , Cell Line, Tumor , Drugs, Chinese Herbal/therapeutic use , Granulocytes/pathology , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Mice , Mice, Inbred C57BL , Myeloid-Derived Suppressor Cells/pathology , Proto-Oncogene Proteins c-bcl-2/physiology , STAT3 Transcription Factor/physiology , Signal Transduction/drug effects , Tumor MicroenvironmentABSTRACT
Chronical hyperuricemia, a severe metabolic disease characterized by increased serum uric acid, urea nitrogen, and creatinine, has a positive correlation with the risks of gouty arthritis, diabetes, hypertension, and kidney damage. Abnormal purine metabolism and reduced uric acid excretion are the major causes of hyperuricemia, which, thus, points to a potential strategy of preventing from or delaying the progress of hyperuricemia-related diseases and its complications by effectively controlling the serum uric acid level. Increasing evidence has revealed that Chinese medicines alleviate hyperuricemia through regulating intestinal flora, which plays a pivotal role in regulating metabolites, including uric acid level. The disease treatment with traditional Chinese medicine is based on syndrome differentiation, and Chinese medicines often have multiple effects and a wide range of targets. In this review, we summarized the anti-hyperuricemia effects and mechanisms of active compounds in Chinese medicines, single Chinese medicinal herbs, and Chinese medicinal prescriptions in regulating the uric acid level via intestinal flora and metabolites, which will be helpful for further study and application of Chinese medicines in hyperuricemia treatment.