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

• DOI: 10.1186/s13046-018-0932-y
• Publication Date: 2018-10-29T14:36:13Z
• Authors: Shengming Deng; Guoxi Zhang; Jiajie Kuai; Peng Fan; Xuexiang Wang; Pei Zhou; Dan Yang; Xichen Zheng; Xiaomei Liu; Qunli Wu; Yuhui Huang
• Keywords: 0301 basic medicine; Lung Neoplasms; Research; T-Lymphocytes; Antiangiogenic therapy; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Mice, Nude; Angiogenesis Inhibitors; Xenograft Model Antitumor Assays; Interferon γ; 3. Good health; Interferon-gamma; Mice; 03 medical and health sciences; Lentinan; Drug resistance; Cell Line, Tumor; Animals; Female; Lung cancer; Colorectal Neoplasms; RC254-282

Abstract Background Antiangiogenic agents are commonly used in lung and colon cancer treatments, however, rapid development of drug resistance limits their efficacy.

Methods 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.

Results 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.

Conclusions 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.