Lentinan inhibits tumor angiogenesis via interferon γ and in a T cell independent manner

• Published in: Journal of experimental & clinical cancer research 2018-10, Vol.37 (1), p.260-12, Article 260
• Main Authors: Deng, Shengming, Zhang, Guoxi, Kuai, Jiajie, Fan, Peng, Wang, Xuexiang, Zhou, Pei, Yang, Dan, Zheng, Xichen, Liu, Xiaomei, Wu, Qunli, Huang, Yuhui
• Format: Article
• Language: English
• Subjects: Angiogenesis; Angiogenesis Inhibitors - administration & dosage; Angiogenesis Inhibitors - pharmacology; Animals; Antiangiogenic therapy; Apoptosis; Cancer therapies; Cell growth; Cell Line, Tumor; Colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Drug resistance; Female; Gastric cancer; Gene expression; Immunotherapy; Interferon γ; Interferon-gamma - genetics; Interferon-gamma - metabolism; Kinases; Laboratory animals; Lentinan; Lentinan - administration & dosage; Lentinan - pharmacology; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lymphocytes; Mice; Mice, Nude; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Tumors; Vascular endothelial growth factor; Xenograft Model Antitumor Assays
• ISSN: 1756-9966; 0392-9078; 1756-9966
• DOI: 10.1186/s13046-018-0932-y

Antiangiogenic agents are commonly used in lung and colon cancer treatments, however, rapid development of drug resistance limits their efficacy. Lentinan (LNT) is a biologically active compound extracted from Lentinus edodes. The effects of LNT on tumor angiogenesis were evaluated by immunohistochemistry in murine LAP0297 lung and CT26 colorectal tumor models. The impacts of LNT on immune cells and gene expression in tumor tissues were determined by flow cytometry, qPCR, and ELISA. Nude mice and IFNγ blockade were used to investigate the mechanism of LNT affecting on tumor angiogenesis. The data sets were compared using two-tailed student's t tests or ANOVA. We found that LNT inhibited tumor angiogenesis and the growth of lung and colon cancers. LNT treatments elevated the expression of angiostatic factors such as IFNγ and also increased tumor infiltration of IFNγ-expressing T cells and myeloid cells. Interestingly, IFNγ blockade, but not T cell deficiency, reversed the effects of LNT treatments on tumor blood vessels. Moreover, long-lasting LNT administration persistently suppressed tumor angiogenesis and inhibited tumor growth. LNT inhibits tumor angiogenesis by increasing IFNγ production and in a T cell-independent manner. Our findings suggest that LNT could be developed as a new antiangiogenic agent for long-term treatment of lung and colon cancers.