Abstract
BackgroundAntiangiogenic agents are commonly used in lung and colon cancer treatments, however, rapid development of drug resistance limits their efficacy.MethodsLentinan (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.ResultsWe 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.ConclusionsLNT 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.
Highlights
Antiangiogenic agents are commonly used in lung and colon cancer treatments, rapid development of drug resistance limits their efficacy
To determine the impact of LNT on tumor angiogenesis, we initially evaluated the dose effects of LNT treatments on LAP0297 lung carcinoma
The results demonstrated that LNT treatments (1 mg/kg) elevated the protein levels of Interferon gamma (IFNγ), Tumor necrosis factor alpha (TNFα), Chemokine ligand 9 (CXCL9), and TIMP metallopeptidase inhibitor 1 (TIMP1) (Additional file 1: Figure S6)
Summary
Antiangiogenic agents are commonly used in lung and colon cancer treatments, rapid development of drug resistance limits their efficacy. Important proangiogenic factors that are known to be involved in tumor angiogenesis include proteins of the vascular endothelial growth factor (VEGF) family, the Antiangiogenic therapies are currently in wide use against non-small cell lung cancer (NSCLC), colorectal cancer, and several other types of solid tumors [1, 3]. The clinical benefits from VEGF inhibitors are modest and transient, Deng et al Journal of Experimental & Clinical Cancer Research (2018) 37:260 and are usually followed by the rapid emergence of drug resistance [1, 3, 6]. A new strategy to better control tumor angiogenesis remains much anticipated
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