Data from: NF-κB pathways are involved in M1 polarization of RAW 264.7 macrophage by polyporus polysaccharide in the tumor microenvironment

Bladder cancer is one of the most malignant tumors closely associated with macrophages. Polyporus polysaccharide (PPS) has shown excellent efficacy in treating bladder cancer with minimal side effects. However, the molecular mechanisms underlying the effects of PPS in inhibiting bladder cancer remain unclear. In this study, we used macrophages cultured alone or with T24 human bladder cancer cell culture supernatant as study models. We found that PPS enhanced the activities of IFN-γ-stimulated RAW 264.7 macrophages, as shown by the release of inducible nitric oxide synthase (INOS), secretion of tumor necrosis factor (TNF)-α and interleukin (IL)-6, phagocytosis activity, as well as expression of M1 phenotype indicators, such as CD40, CD284 and CD86. PPS acted upstream in activation cascade of nuclear factor (NF)-κB signaling pathways by interfering with IκB phosphorylation. In addition, PPS regulated NF-κB (P65) signaling by interfering with Toll-like receptor (TLR)-4, INOS and cyclooxygenase (COX)-2. Our results indicate that PPS activates macrophages through TLR4/NF-κB signaling pathways.

膀胱癌是与巨噬细胞密切相关的恶性程度最高的肿瘤之一。猪苓多糖（Polyporus polysaccharide, PPS）在膀胱癌治疗中展现出优异疗效且副作用极低，但其抑制膀胱癌的分子机制尚未明确。本研究以单独培养的巨噬细胞，或与人类膀胱癌T24细胞培养上清液共培养的巨噬细胞作为研究模型。研究发现，PPS可增强干扰素γ（IFN-γ）刺激后的RAW 264.7巨噬细胞活性，具体表现为诱导型一氧化氮合酶（inducible nitric oxide synthase, INOS）的释放、肿瘤坏死因子α（tumor necrosis factor, TNF-α）与白细胞介素6（interleukin, IL-6）的分泌、吞噬活性提升，以及CD40、CD284、CD86等M1表型标志物的表达上调。PPS通过干扰IκB磷酸化，作用于核因子κB（nuclear factor, NF-κB）信号通路激活级联的上游环节。此外，PPS还可通过干预Toll样受体4（Toll-like receptor, TLR-4）、INOS与环氧合酶2（cyclooxygenase, COX-2），调控NF-κB（P65）信号通路。本研究结果表明，PPS可通过TLR4/NF-κB信号通路激活巨噬细胞。