Dataset Information

NF-?B pathways are involved in M1 polarization of RAW 264.7 macrophage by polyporus polysaccharide in the tumor microenvironment.

ABSTRACT: 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-?-stimulated RAW 264.7 macrophages, as shown by the release of inducible nitric oxide synthase (INOS), secretion of tumor necrosis factor (TNF)-? 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)-?B signaling pathways by interfering with I?B phosphorylation. In addition, PPS regulated NF-?B (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-?B signaling pathways.

SUBMITTER: Liu CP

PROVIDER: S-EPMC5695768 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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

Liu Chun-Ping CP Zhang Xian X Tan Qing-Long QL Xu Wen-Xing WX Zhou Chang-Yuan CY Luo Min M Li Xiong X Huang Run-Yue RY Zeng Xing X

PloS one 20171120 11

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 RA ...[more]

PMID: 29155869

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Project description:Baicalein is one of the bioactive compounds extracted from Scutellaria baicalensis. Recent studies indicated the antitumor effects of baicalein, however, the underlying mechanisms are needed to be further determined. In this study, we found that baicalein could inhibit the tumor growth in mice models of breast cancer and melanoma and worked as an immunomodulator to promote the infiltration of tumor-associated macrophages (TAMs) and skew the TAMs towards the M1-like phenotype. Baicalein also induced M1-like phenotype polarization in THP-1-derived macrophages. Meanwhile, the expression of pro-inflammatory factors associated with M1 macrophages, including TNF-α, IL-1β, CXCL9 and CXCL10, were increased after baicalein treatment. Mechanistically, the RNA-seq data suggested that baicalein potentiated the M1 macrophage polarization via the NF-κB/TNF-α signaling pathway. ELISA and confocal microscopy assay confirmed that baicalein significantly induced the production of TNF-α and the activation of NF-κB, while TNF-α neutralization inhibited baicalein-induced macrophage polarization toward M1, and NF-κB P65 knock-down suppressed baicalein-induced TNF-α production in THP-1-derived macrophages. Phosphoinositide 3-kinase (PI3k) γ has been reported as a key molecule in macrophage polarization, and inhibition of PI3Kγ activates the NF-κB-related inflammatory signals. Our pharmacological network analysis predicted that PI3Kγ might be one of the major targets of baicalein. The results from the docking program and surface plasmon resonance (SPR) confirmed that baicalein displayed good binding activity to PI3Kγ. We further found that baicalein not only exhibited a direct inhibitory effect on the protein kinase activity of PI3Kγ, but also reduced the mRNA and protein expression of PI3Kγ, indicating that baicalein might be a novel PI3Kγ inhibitor. In summary, baicalein mediated the TAMs skewing to M1-TAMs, and then retarded tumor growth. These effects, at least in part, were linked to the PI3Kγ/NF-κB signaling.

Project description:BackgroundPolyporus polysaccharide (PPS), an active ingredient of traditional Chinese medicinal Polyporus umbellatus, has multiple biological functions, such as anti-cancer, immune-regulating and hepatoprotective activities. The purpose of this study was to investigate the mechanism of homogeneous polyporus polysaccharide (HPP) activated macrophages in the treatment of bladder cancer.Methods100 ng/mL Phorbol myristate acetate (PMA) was used to induce THP-1 human leukemic cells as a macrophage model. Then macrophages derived from THP-1 were treated with different concentrations of HPP (1, 10 and 100 μg/mL). Flow cytometry and RT-PCR were used to detected the expression of CD16, CD23, CD86, CD40 and interleukin (IL)-Iβ, iNOS mRNA. ELISA was used to test the change of IL-1β and TNF-α in macrophage after the treatment with HPP. The conditioned medium from HPP-polarized macrophages was used to detect the effect of activated macrophages on bladder cancer. MTT assay, 5-ethynyl-2'-deoxyuridine assay, flow cytometry, Transwell assay, and Western blot analysis were used to detect the effects of polarized macrophages on the viability, proliferation, apoptosis, and migration of bladder cancer cells. Western blot was also used to analysis the change of JAK2/NF-κB pathway protein.ResultsHPP promoted the expression of pro-inflammatory factors, such as IL-Iβ, TNF-α and iNOS, and surface molecules CD86, CD16, CD23, and CD40 in macrophages and then polarized macrophages to M1 type. Results demonstrated that activated macrophages inhibited the proliferation of bladder cancer cells, regulated their apoptosis, and inhibited migration and epithelial-mesenchymal transformation (EMT). JAK2/NF-κB pathways were downregulated in the anti-bladder cancer process of activated macrophages.ConclusionThe findings indicated that HPP inhibited the proliferation and progression of bladder cancer by the polarization of macrophages to M1 type, and JAK2/NF-κB pathway was downregulated in the process of anti-bladder cancer.

Dataset Information

NF-?B pathways are involved in M1 polarization of RAW 264.7 macrophage by polyporus polysaccharide in the tumor microenvironment.

Publications

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

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