Oxymatrine‑mediated maturation of dendritic cells leads to activation of FOXP3+/CD4+ Treg cells and reversal of cisplatin‑resistance in lung cancer cells

• Published in: Molecular medicine reports Vol. 19; no. 5; pp. 4081 - 4090
• Main Authors: Liu, Hui, Zou, Manman, Li, Pei, Wang, Haifeng, Lin, Xijun, Ye, Jin
• Format: Journal Article
• Language: English
• Published: Greece Spandidos Publications UK Ltd 01.05.2019; D.A. Spandidos
• Subjects: A549 Cells; Adult; Alkaloids - pharmacology; Annexin V; Antigens; Antigens, CD - metabolism; Antitumor activity; Apoptosis; Apoptosis - drug effects; Cancer therapies; Cardiovascular disease; Case-Control Studies; CD11 antigen; CD4 antigen; CD4 Antigens - metabolism; CD83 Antigen; CD86 antigen; Cell activation; Cell culture; Cell cycle; Cells, Cultured; Chemotherapy; Cisplatin; Cisplatin - pharmacology; Cytokines; Cytokines - metabolism; Cytotoxicity; Dendritic cells; Dendritic Cells - cytology; Dendritic Cells - drug effects; Dendritic Cells - immunology; Drug Resistance, Neoplasm - drug effects; Enzyme-linked immunosorbent assay; Experiments; Flow cytometry; Forkhead protein; Forkhead Transcription Factors - metabolism; Foxp3 protein; Gene expression; Hepatitis; Humans; Immunoglobulins - metabolism; Immunosuppression; Immunotherapy; Inflammation; Interleukin 12; Interleukin 2; Lung cancer; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Lymphocyte Activation - drug effects; Lymphocytes; Lymphocytes T; Male; Maturation; Membrane Glycoproteins - metabolism; Middle Aged; Proto-Oncogene Proteins c-bcl-2 - metabolism; Quinolizines - pharmacology; Radiation therapy; Systemic diseases; T-Lymphocytes, Regulatory - cytology; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Tumor cells; Tumors; γ-Interferon; United States > US; China
• ISSN: 1791-2997; 1791-3004
• DOI: 10.3892/mmr.2019.10064

The dendritic cell (DC)‑regulatory T (Treg) system serves a leading role in the immunosuppression of the tumor microenvironment, which is not conducive to radiotherapy and chemotherapy treatment for lung cancer. The present study aimed to investigate the effect of oxymatrine (OMT) on the DC‑Treg system in the tumor microenvironment in vitro and to examine its mechanism. The expressions of CD83 antigen, T‑lymphocyte activation antigen CD86, CD11 antigen‑like family member C and major histocompatibility complex II in DCs were increased upon treatment with 1 mg/ml OMT, as detected by flow cytometry. Following pretreatment with OMT, the DCs mediated the forkhead box protein P3 overexpression in primitive cluster of differentiation 4+ T cells at the protein and mRNA expression levels. The expression levels of anti‑inflammatory factors, including interleukin (IL)‑10, tumor growth factor‑β, IL‑35, and pro‑inflammatory cytokines, including interferon‑γ, IL‑12 and IL‑2, in the co‑culture supernatant were increased as measured by ELISA. When DCs and DC‑Tregs were co‑cultured with cisplatin‑resistant A549 cells, the proportion of apoptosis in the co‑culture groups was increased under treatment with cisplatin, which was detected by Annexin V/propidium Iodide staining and western blotting. The present results suggested that OMT may promote the maturation of DCs, mediate the differentiation of T cells into Treg cells, and reverse the resistance of tumor cells to cisplatin in vitro. It was suggested that OMT is an important adjunct to chemotherapy through the regulation of antitumor responses.