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The biological macromolecule Nocardia rubra cell‐wall skeleton as an avenue for cell‐based immunotherapy
Author(s) -
Meng Yiming,
Sun Jing,
Wang Xiaonan,
Ma Yushu,
Kong Cuicui,
Zhang Guirong,
Dou Heng,
Nan Ning,
Shi Mingsheng,
Yu Tao,
Piao Haozhe
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.28182
Subject(s) - propidium iodide , biology , cancer research , apoptosis , immunotherapy , immune system , cell , cytotoxicity , immunology , programmed cell death , in vitro , biochemistry , genetics
Promoting the antitumor effects of cell‐based immunotherapy for clinical application remains a difficult challenge. Nocardia rubra cell‐wall skeleton (N‐CWS) is an immunotherapeutic agent for cancers that have been proven to possess the ability to activate immune response without showing toxicity. However, its effects on immune cells that are derived from tumor patients and cultured in vitro remain unclear. As expected, N‐CWS can enhance the proliferation and viability of cytokine‐induced killer (CIK) cells, dendritic cells (DCs), and natural killer (NK) cells. The maturation of DCs and specific cytotoxicity against NK cells and CIK cells were consistently promoted. The TUNEL‐staining and the Annexin V/propidium iodide assay revealed that after treatment with N‐CWS, the stimulated CIK/NK cells could induce DNA breaks in tumor cells. Furthermore, quantitative real‐time polymerase chain reaction and western blot analysis showed upregulation of proapoptotic biomarkers (caspase‐3 and caspase‐9) and a downregulation of the antiapoptotic biomarker Bcl‐2 in the tumor cells of the N‐CWS‐treated group, indicating that N‐CWS could induce hepatocellular carcinoma cell apoptosis via CIK/NK cells. Finally, CIK/NK cells could notably suppress the invasion and migration of tumor cells in the presence of N‐CWS. Our study provides evidence that N‐CWS could significantly increase the growth of CIK cells, DCs, and NK cells, particularly due to its robust antitumor activities by inducing apoptosis, and attenuate the invasion and migration of tumor cells.