Abstract
A homogeneous polysaccharide (GLP), with an average molecular weight of 4.44 × 104 Da, was isolated and purified from the fruiting bodies of Ganoderma lucidum. In this work, we examined the antitumor activities of GLP using a mouse Lewis lung cancer (LLC) model and explored possible molecular pathways involved in its immunomodulatory mechanism on tumor–host interaction. GLP administration (25 and 100 mg/kg) significantly inhibited tumor growth, as evidenced by the decreased tumor volume and tumor weight, as well as histological features of tumor tissues with concomitant down-regulation of proliferating cell nuclear antigen (PCNA) proliferative marker. Less myeloid-derived suppressor cells (MDSCs) were accumulated in both spleen and tumor tissues from GLP-treated mice. In contrast, the percentage of CD4+ and CD8+ T cells together with the production of Th1-type cytokines (IFN-γ and IL-12) was increased in the spleen of LLC-bearing mice following GLP administration. Furthermore, GLP administration reversed the attenuated expression of CARD9, p-Syk and p-p65, and increased indoleamine 2,3-dioxygenase (IDO) protein expression in MDSCs of LLC-bearing mice. Collectively, our data demonstrated the first time that GLP induced the differentiation of MDSCs and inhibited the accumulation of MDSCs via CARD9-NF-κB-IDO pathway, thus prevented lung cancer development.
Highlights
Lung cancer is one of the most concerned health challenges due to its high morbidity and mortality, and new cases number are rising worldwide [1]
Antibodies against proliferating cell nuclear antigen (PCNA), caspase recruitment domain-containing protein 9 (CARD9), phosphorylated Syk (p-Syk), p-p65, indoleamine 2,3-dioxygenase (IDO) and β-actin as well as horseradish peroxidase (HRP)-conjugated secondary antibodies were obtained from Santa Cruz Biotechnology (SantaCruz, CA)
Crude polysaccharide fraction crude G. lucidum polysaccharide (CGLP) was isolated from the fruiting bodies of G. lucidum with a yield of 8.65% by 95% ethanol reflux extraction, hot water extraction, ethanol precipitation, Sevag reagent extraction and dialysis
Summary
Lung cancer is one of the most concerned health challenges due to its high morbidity and mortality, and new cases number are rising worldwide [1]. It is evident that current conventional treatments including surgery, radiation and chemotherapy have limited effectiveness and the prognosis remains mediocre in operated patients [4,5]. Discovering novel anticancer drugs with less side effects and new strategies for the treatment of lung cancer are so much impending. Immunotherapy provides a new approach for lung cancer treatment [6]. Recent studies have suggested that myeloid-derived suppressor cells (MDSCs) accumulate in tumor-bearing hosts and are the major suppressor of the immune responses, which hampers effective immunotherapeutic approaches [8]. Screening for drugs with the ability to inhibit the deposition of MDSCs in tumor-bearing patients has received tremendous scientific attention in cancer research.
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